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1. Risk factors and action thresholds for the novel coronavirus pandemic. Insights from the Italian Society of Nephrology COVID-19 Survey

Author

Nordio, M., Reboldi, G., Di Napoli, A., Quintaliani, G., Alberici, F., Postorino, M., Aucella, F., Messa, P., Brunori, G., Bosco, M., Malberti, F., Mandreoli, M., Mazzaferro, S., Movilli, E., Ravera, M., Salomone, M., Santoro, D., Postorinolimido, M. A., Bonomini, M., Stingone, A., Maccarone, M., Di Loreto, E., Stacchiotti, L., Malandra, R., Chiarella, S., D'Agostino, F., Fuiano, G., Nicodemo, L., Bonofiglio, R., Greco, S., Mallamaci, F., Barreca, E., Caserta, C., Bruzzese, V., Galati, D., Tramontana, D., Viscione, M., Chiuchiolo, L., Tuccillo, S., Sepe, M., Vitale, F., Ciriana, E., Martignetti, V., Caserta, D., Stizzo, A., Romano, A., Iulianiello, G., Cascone, E., Minicone, P., Chiricone, D., Delgado, G., Barbato, A., Celentano, S., Molfino, I., Coppola, S., Raiola, I., Abategiovanni, M., Borrelli, S., Margherita, C., Bruno, F., Ida, M., Aliperti, E., Potito, D., Cuomo, G., De Luca, M., Merola, M., Botta, C., Garofalo, G., Alinei, P., Paglionico, C., Roano, M., Vitale, S., Ierardi, R., Fimiani, V., Conte, G., Di Natale, G., Romano, M., Di Marino, V., Scafarto, A., Meccariello, S., Pecoraro, C., Di Stazio, E., Di Meglio, E., Cuomo, A., Maresca, B., Rotaia, E., Capasso, G., Auricchio, M., Pluvio, C., Maddalena, L., De Maio, A., Palladino, G., Buono, F., Gigliotti, G., Mancini, E., La Manna, G., Storari, A., Mosconi, G., Cappelli, G., Scarpioni, R., Gregorini, M., Rigotti, A., Mancini, W., Bianco, F., Boscutti, G., Amici, G., Tosto, M., Fini, R., Pace, G., Cioffi, A., Boccia, E., Di Lullo, L., Di Zazzo, G., Simonelli, R., Bondatti, F., Miglio, L., Rifici, N., Treglia, A., Muci, M., Baldinelli, G., Rizzi, E., Lonzi, M., De Cicco, C., Forte, F., De Paolis, P., Grandaliano, Giuseppe, Cuzziol, C., Torre, V. M., Sfregola, P., Rossi, V., Fabio, G., Flammini, A., Filippini, A., Onorato, L., Vendola, F., Di Daniela, N., Alfarone, C., Scabbia, L., Ferrazzano, M., Grotta, B. D., Gamberini, M., Fazzari, L., Mene, P., Morgia, A., Catucci, A., Palumbo, R., Puliti, M., Marinelli, R., Polito, P., Marrocco, F., Morabito, S., Rocca, R., Nazzaro, L., Lavini, R., Iamundo, V., Chiappini, M., Casarci, M., Morosetti, M., Hassan, S., Firmi, G., Galliani, M., Serraiocco, M., Feriozzi, S., Valentini, W., Sacco, P., Garibotto, G., Cappelli, V., Saffioti, C., Repetto, M., Rolla, D., Lorenz, M., Pedrini, L., Polonioli, D., Galli, E., Ruggenenti, P., Scolari, F., Bove, S., Costantino, E., Bracchi, M., Mangano, S., Depetri, G., La Milia, V., Farina, M., Zecchini, S., Savino, R., Melandri, M., Guastoni, C., Paparella, M., Gallieni, M., Minetti, E., Bisegna, S., Righetti, M., Badalamenti, S., Alberghini, E., Bertoli, S., Fabbrini, P., Albrizio, P., Rampino, T., Colturi, C., Rombola, G., Lucatello, A., Guerrini, E., Ranghino, A., Lenci, F., Fanciulli, E., Santarelli, S., Damiani, C., Garofalo, D., Sopranzi, F., Santoferrara, A., Di Luca, M., Galiotta, P., Brigante, M., Manganaro, M., Maffei, S., Berto, I., Besso, L., Viglino, G., Cusinato, S., Chiarinottichiappero, D. F., Tognarelli, G., Gianoglio, B., Forneris, G., Biancone, L., Savoldi, S., Vitale, C., Boero, R., Filiberti, O., Borzumati, M., Gesualdo, L., Lomonte, C., Gernone, G., Pallotta, G., Di Paolo, S., Vernaglione, L., Specchio, A., Stallone, G., Dell'Aquila, R., Sandri, G., Russo, F., Napoli, M., Marangi, A., Morrone, L., Di Stratis, C., Fresu, A., Cicu, F., Murtas, S., Manca, O., Pani, A., Pilloni, M., Pistis, R., Cadoni, M., Contu, B., Logias, F., Ivaldi, R., Fancello, S., Cossu, M., Lepori, G., Vittoria, S., Battiati, E., Arnone, M., Rome, M., Barbera, A., Granata, A., Collura, G., Dico, C. L., Pugliese, G., Di Natale, E., Rizzari, G., Cottone, L., Longo, N., Battaglia, G., Marcantoni, C., Giannetto, G., Tumino, G., Randazzo, F., Bellissimo, L., Faro, F. L., Grippaldi, F., Urso, S., Quattrone, G., Todaro, I., Vincenzo, D., Murgo, A., Masuzzo, M., Pisacane, A., Monardo, P., Pontorierro, M., Quari, C., Bauro, A., Chimenz, R. R., Alfio, D., Girasole, F., Cascio, A. L., Caviglia, A., Tornese, F., Sirna, F., Altieri, C., Cusumano, R., Saveriano, V., La Corte, A., Locascio, G., Rotolo, U., Musso, S., Risuglia, L., Blanco, G., Minardo, G., Castellino, S., Zappulla, Z., Randone, S., Di Francesca, M., Cassetti, C. C., Oddo, G., Buscaino, G., Mucaria, F., Barraco, V. I., Di Martino, A., Rallo, D., Dani, L., Campolo, G., Manescalchi, F., Biagini, M., Agate, M., Panichi, V., Casani, A., Traversari, L., Garosi, G., Tabbi, M., Selvi, A., Cencioni, L., Fagugli, R., Timio, F., Leveque, A., Manes, M., Mennella, G., Calo, L., Fiorini, F., Abaterusso, C., Calzavara, P., Meneghel, G., Bonesso, C., Gambaro, G., Gammaro, L., Rugiu, C., Ronco, C., Nordio M., Reboldi G., Di Napoli A., Quintaliani G., Alberici F., Postorino M., Aucella F., Messa P., Brunori G., Bosco M., Malberti F., Mandreoli M., Mazzaferro S., Movilli E., Ravera M., Salomone M., Santoro D., PostorinoLimido M.A., Bonomini M., Stingone A., Maccarone M., Di Loreto E., Stacchiotti L., Malandra R., Chiarella S., D'Agostino F., Fuiano G., Nicodemo L., Bonofiglio R., Greco S., Mallamaci F., Barreca E., Caserta C., Bruzzese V., Galati D., Tramontana D., Viscione M., Chiuchiolo L., Tuccillo S., Sepe M., Vitale F., Ciriana E., Martignetti V., Caserta D., Stizzo A., Romano A., Iulianiello G., Cascone E., Minicone P., Chiricone D., Delgado G., Barbato A., Celentano S., Molfino I., Coppola S., Raiola I., Abategiovanni M., Borrelli S., Margherita C., Bruno F., Ida M., Aliperti E., Potito D., Cuomo G., De Luca M., Merola M., Botta C., Garofalo G., Alinei P., Paglionico C., Roano M., Vitale S., Ierardi R., Fimiani V., Conte G., Di Natale G., Romano M., Di Marino V., Scafarto A., Meccariello S., Pecoraro C., Di Stazio E., Di Meglio E., Cuomo A., Maresca B., Rotaia E., Capasso G., Auricchio M., Pluvio C., Maddalena L., De Maio A., Palladino G., Buono F., Gigliotti G., Mancini E., La Manna G., Storari A., Mosconi G., Cappelli G., Scarpioni R., Gregorini M., Rigotti A., Mancini W., Bianco F., Boscutti G., Amici G., Tosto M., Fini R., Pace G., Cioffi A., Boccia E., Di Lullo L., Di Zazzo G., Simonelli R., Bondatti F., Miglio L., Rifici N., Treglia A., Muci M., Baldinelli G., Rizzi E., Lonzi M., De Cicco C., Forte F., De Paolis P., Grandaliano G., Cuzziol C., Torre V.M., Sfregola P., Rossi V., Fabio G., Flammini A., Filippini A., Onorato L., Vendola F., Di Daniela N., Alfarone C., Scabbia L., Ferrazzano M., Grotta B.D., Gamberini M., Fazzari L., Mene P., Morgia A., Catucci A., Palumbo R., Puliti M., Marinelli R., Polito P., Marrocco F., Morabito S., Rocca R., Nazzaro L., Lavini R., Iamundo V., Chiappini M., Casarci M., Morosetti M., Hassan S., Firmi G., Galliani M., Serraiocco M., Feriozzi S., Valentini W., Sacco P., Garibotto G., Cappelli V., Saffioti C., Repetto M., Rolla D., Lorenz M., Pedrini L., Polonioli D., Galli E., Ruggenenti P., Scolari F., Bove S., Costantino E., Bracchi M., Mangano S., Depetri G., La Milia V., Farina M., Zecchini S., Savino R., Melandri M., Guastoni C., Paparella M., Gallieni M., Minetti E., Bisegna S., Righetti M., Badalamenti S., Alberghini E., Bertoli S., Fabbrini P., Albrizio P., Rampino T., Colturi C., Rombola G., Lucatello A., Guerrini E., Ranghino A., Lenci F., Fanciulli E., Santarelli S., Damiani C., Garofalo D., Sopranzi F., Santoferrara A., Di Luca M., Galiotta P., Brigante M., Manganaro M., Maffei S., Berto I., Besso L., Viglino G., Cusinato S., ChiarinottiChiappero D.F., Tognarelli G., Gianoglio B., Forneris G., Biancone L., Savoldi S., Vitale C., Boero R., Filiberti O., Borzumati M., Gesualdo L., Lomonte C., Gernone G., Pallotta G., Di Paolo S., Vernaglione L., Specchio A., Stallone G., Dell'Aquila R., Sandri G., Russo F., Napoli M., Marangi A., Morrone L., Di Stratis C., Fresu A., Cicu F., Murtas S., Manca O., Pani A., Pilloni M., Pistis R., Cadoni M., Contu B., Logias F., Ivaldi R., Fancello S., Cossu M., Lepori G., Vittoria S., Battiati E., Arnone M., Rome M., Barbera A., Granata A., Collura G., Dico C.L., Pugliese G., Di Natale E., Rizzari G., Cottone L., Longo N., Battaglia G., Marcantoni C., Giannetto G., Tumino G., Randazzo F., Bellissimo L., Faro F.L., Grippaldi F., Urso S., Quattrone G., Todaro I., Vincenzo D., Murgo A., Masuzzo M., Pisacane A., Monardo P., Pontorierro M., Quari C., Bauro A., Chimenz R.R., Alfio D., Girasole F., Cascio A.L., Caviglia A., Tornese F., Sirna F., Altieri C., Cusumano R., Saveriano V., La Corte A., Locascio G., Rotolo U., Musso S., Risuglia L., Blanco G., Minardo G., Castellino S., Zappulla Z., Randone S., Di Francesca M., Cassetti C.C., Oddo G., Buscaino G., Mucaria F., Barraco V.I., Di Martino A., Rallo D., Dani L., Campolo G., Manescalchi F., Biagini M., Agate M., Panichi V., Casani A., Traversari L., Garosi G., Tabbi M., Selvi A., Cencioni L., Fagugli R., Timio F., Leveque A., Manes M., Mennella G., Calo L., Fiorini F., Abaterusso C., Calzavara P., Meneghel G., Bonesso C., Gambaro G., Gammaro L., Rugiu C., and Ronco C.

Subjects
Male, Contextual analysis, medicine.medical_treatment, Population, 030232 urology & nephrology, Recursive partitioning, 030204 cardiovascular system & hematology, Rate ratio, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Classification tree, COVID-19, Renal replacement therapy, Risk Factors, Medical, Surveys and Questionnaires, Health care, medicine, Settore MED/14 - NEFROLOGIA, Humans, education, Pandemics, Societies, Medical, Female, Italy, Nephrology, education.field_of_study, business.industry, Multilevel model, Decision rule, Confidence interval, Original Article, Hemodialysis, business, Contextual analysi, Societies, Demography
Abstract

Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

Published
2021

2. Development and validation of the perception of housing quality scale (PHQS)

Author

Caffaro, F., Galati, D., Roccato, Michele, Caffaro, F., Galati, D., and Roccato, M.

Subjects
Quality of life, Measurement, Perception of housing quality, Housing, Indoor environment
Abstract

In this study, we aimed to develop and validate the Perception of Housing Quality Scale (PHQS), a multi-item, multi-factorial measure of perceived housing quality focused on peoples homes as the unit of analysis and based on individuals perceptions of how much the physical aspects of their home environments fulfill their daily needs. The instrument was developed by a multidisciplinary team comprising psychologists and architects for the identification of the main factors describing the perceived quality of the physical features of home environments. Confirmatory factor analysis performed on the data, collected from a quota sample comprising 285 Italian adults aged between 25 and 65 (women = 52.3%, Mage = 42.81, SD = 12.73), confirmed the hypothesis that two correlated factors define perceived housing quality: "Indoor environment and architectural design" and "Outdoor stressors." These factors revealed the expected correlations with home ownership and the discrepancy between the actual and the ideal home. The implications of this scale in housing research are discussed.

Published
2016

3. Distinct pathways of neural coupling for different basic emotions

Author

Tettamanti, M, Rognoni, E, Cafiero, R, Costa, T, Galati, D, Perani, D, Tettamanti, M., Rognoni, E., Cafiero, R., Costa, T., Galati, D., Perani, D., Tettamanti, M, Rognoni, E, Cafiero, R, Costa, T, Galati, D, Perani, D, Tettamanti, M., Rognoni, E., Cafiero, R., Costa, T., Galati, D., and Perani, D.

Abstract

Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience.

Published
2012

4. The effects of religious involvement on short-term psychological reactions to the death of Pope John Paul II: A study on an italian sample

Author

Schmidt, S, Sotgiu, I, Tinti, C, Curci, A, Businaro, N, Galati, D, Galati, D., BUSINARO, NICOLETTA, Schmidt, S, Sotgiu, I, Tinti, C, Curci, A, Businaro, N, Galati, D, Galati, D., and BUSINARO, NICOLETTA

Abstract

The short-term psychological reactions to the death of Pope John Paul II were investigated. Between 1 to 6 days after this event, 526 Catholic and atheist Italian adults took part in a questionnaire study. Participants were asked to report the personal circumstances in which they first learned about the Pope's death, their emotional reactions, and their appraisal of the event's importance and consequentiality. Other questions assessed immediate memory for the original event, surprise-expectedness, exposure to mass media, and religious involvement. Results showed that the news of the Pope's death, although widely expected, had a strong cognitive and emotional impact. Almost all the participants were able to recall the personal circumstances in which they heard the news. A positive relation was observed between the degree of religious involvement and appraisal of importance and consequentiality, intensity of emotion, memory for event-related details, and frequency of exposure to mass media. Effects related to the age of the participants were also found. © Society for Personality Research (Inc.).

Published
2007

5. Limited usefulness of QuantiFERON-TB Gold In-Tube for monitoring anti-tuberculosis therapy

Author

BOCCHINO, MARIALUISA, BRUZZESE, DARIO, SANDUZZI ZAMPARELLI, ALESSANDRO, Chairadonna P., Matarese A., Salvatores M., Tronci M., Moscariello E., Galati D., Alma M.G., Altieri A.M., Bocchino, Marialuisa, Chiaradonna, P, Matarese, A., Bruzzese, Dario, Salvatores, M., Tronci, M., Moscariello, E., Galati, D., Alma, M. G., SANDUZZI ZAMPARELLI, Alessandro, Altieri, A. M., and Chairadonna, P.

Subjects
Tuberculosi, Treatment monitoring, Interferon-gamma release assay, Serial testing
Published
2010

14. Le 'occasioni' di tristezza e rabbia in età evolutiva.

Author

Barone, L., Galati, D., Marchetti, Antonella, Marchetti, Antonella (ORCID:0000-0001-9985-0539), Barone, L., Galati, D., Marchetti, Antonella, and Marchetti, Antonella (ORCID:0000-0001-9985-0539)

Abstract

Not available.

Published
1992

17. Fc gamma receptor IIIa polymorphisms in advanced colorectal cancer patients correlated with response to anti-EGFR antibodies and clinical outcome

Author

Calemma Rosa, Ottaiano Alessandro, Trotta Anna, Nasti Guglielmo, Romano Carmela, Napolitano Maria, Galati Domenico, Borrelli Pasquale, Zanotta Serena, Cassata Antonino, Castello Giuseppe, Iaffaioli Vincenzo, and Scala Stefania

Subjects
Fc gamma receptor, Colorectal cancer, Prognosis, Cetuximab, Panitumumab, Antibody-dependent cell-mediated cytotoxicity, Medicine
Abstract

Abstract Background Anti-EGFR monoclonal antibodies have shown efficacy in the treatment of metastatic colorectal cancer (mCRC). One of the mechanism is the antibody-dependent cell-mediated cytotoxicity (ADCC) in which Fc region of the antibody binds to the Fc gamma receptors (FcγR) expressed by immune cells. The present study investigated the association between single nucleotide polymorphisms of FcγRIIa and FcγRIIIa and clinical outcome in mCRC treated with anti-EGFR antibodies. Methods Seventy-four consecutive patients with mCRC were analyzed. The genotypes for FcγRIIa-131 histidine (H)/arginine (R), FcγRIIIa-158 valine (V)/phenylanaline (F) polymorphisms were evaluated by directly sequencing. Multiplex allele-specific polymerase chain reaction was performed for FcγRIIIa-158 valine (V)/phenylanaline (F). Correlations between FcγR polymorphisms, baseline patient and tumor features were studied by contingency tables and the chi-square test. The Kaplan-Meier product limit method was applied to the progression-free survival (PFS) curves. Univariate analysis was performed with the log-rank test. Cox proportional-hazards regression was used to analyze the effect of multiple risk factors on PFS. Results FcγRIIIa polymorphisms were significantly associated with response to anti-EGFR-based therapy in 49 patients with kras wt tumors (p=0.035). There was not association with response for FcγRIIa polymorphisms. Furthermore, obtained results suggested that prognosis is particularly unfavorable for patients carrying the FcγRIIIa-158F/F genotype (median PFS V/V, V/F, F/F: 18.2 vs 17.3 vs 9.4 months). No prognostic ability was identified for FcγRIIa polymorphisms. Conclusions In mCRC patients the presence of FcγRIIIa-F can predict resistance to anti-EGFR therapy and unfavorable prognosis.

Published
2012
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18. Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Author

Domenico Galati, Serena Zanotta, Mariaelena Capone, Gabriele Madonna, Domenico Mallardo, Marilena Romanelli, Ester Simeone, Lucia Festino, Francesca Sparano, Rosa Azzaro, Rosaria De Filippi, Antonio Pinto, Chrystal M. Paulos, Paolo A. Ascierto, Galati, D, Zanotta, S, Capone, M, Madonna, G, Mallardo, D, Romanelli, M, Simeone, E, Festino, L, Sparano, F, Azzaro, R, De Filippi, R, Pinto, A, Paulos, Cm, and Ascierto, Pa

Subjects
Nivolumab, PD1-Ab, Cancer biomarker, General Medicine, Flow cytometry, Immunotherapy, Melanoma, General Biochemistry, Genetics and Molecular Biology, CD26
Abstract

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe off-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will benefit from anti-PD-1 treatment avoiding unwanted side effects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multi-parametric flow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were significantly reduced in melanoma patients compared to healthy subjects (p = 0.001). In addition, a significant association was observed between a low baseline percentage of CD4+CD26high T cells (+CD26high T cells than patients with non-clinical benefit (p = 0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p = 0.014) and best Overall Response Rate (p = 0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were significantly higher in comparison with the frequencies measured at W0 (p Conclusions Our study firstly demonstrates that peripheral blood circulating CD4+CD26high T lymphocytes represent potential biomarkers whose perturbations are associated with reduced survival and worse clinical outcomes in melanoma patients.

Published
2023

19. Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection

Author

Giuseppe Gelsomino, Alfredo Salerno, Simone A. Joosten, Alessandro Sanduzzi, Domenico Galati, Francesco Dieli, Giuliana Guggino, Alessandro Matarese, Willeke P. J. Franken, Tom H. M. Ottenhoff, Paola Di Carlo, Lucina Titone, Nadia Caccamo, Marialuisa Bocchino, Caccamo N, Guggino G, Joosten SA, Gelsomino G, Di Carlo P, Titone Lanza di Scalea L, Galati D, Bocchino M, Matarese A, Salerno A, Sanduzzi A, Franken WP, Ottenhoff TH, Dieli F, Caccamo, N., Guggino, G., Joosten, S. A., Gelsomino, G., Di Carlo, P., Titone, L., Galati, D., Bocchino, Marialuisa, Matarese, A., Salerno, A., SANDUZZI ZAMPARELLI, Alessandro, Franken, W. P., Ottenhoff, T. H., and Dieli, F.

Subjects
Interleukin 2, Adult, CD4-Positive T-Lymphocytes, Male, Tuberculosis, Settore MED/17 - Malattie Infettive, Immunology, Cell Separation, Biology, Lymphocyte Activation, Flow cytometry, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Bacterial Proteins, CD4(+) T cells Cytokines Mycobacterium tuberculosis infection Tuberculosis disease interferon-gamma immunological memory disease responses protection cytokine immunity bcg vaccination virus, medicine, Immunology and Allergy, Distribution (pharmacology), Humans, Cytokine, Tuberculosis, Pulmonary, 030304 developmental biology, Tuberculosis disease, Settore MED/04 - Patologia Generale, 0303 health sciences, Antigens, Bacterial, medicine.diagnostic_test, Mycobacterium tuberculosis infection, Middle Aged, biology.organism_classification, medicine.disease, Flow Cytometry, Phenotype, Virology, CD4+ T cells, Bacterial Load, 3. Good health, Acute Disease, Chronic Disease, Cytokines, Tumor necrosis factor alpha, Acyltransferases, 030215 immunology, medicine.drug
Abstract

Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametic flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.

Published
2010

20. A bird's eye view on the role of dendritic cells in SARS-CoV-2 infection: Perspectives for immune-based vaccines

Author

Ludovica Capitelli, Serena Zanotta, Marialuisa Bocchino, Domenico Galati, Galati, Domenico, Zanotta, Serena, Capitelli, Ludovica, Bocchino, Marialuisa, Galati, D., Zanotta, S., Capitelli, L., and Bocchino, M.

Subjects
dendritic cell, Immunology, Review Article, medicine.disease_cause, SARS‐CoV‐2, Pathogenesis, Immune system, COVID‐19, immune‐therapies, Pandemic, medicine, Immunology and Allergy, Humans, dendritic cells, Pandemics, Review Articles, Coronavirus, Vaccines, Innate immune system, business.industry, SARS-CoV-2, COVID-19, Acquired immune system, medicine.disease, immune-therapie, business, Cytokine storm, Pneumonia (non-human)
Abstract

Coronavirus disease‐19 (COVID‐19) is a complex disorder caused by the pandemic diffusion of a novel coronavirus named SARS‐CoV‐2. Clinical manifestations vary from silent infection to severe pneumonia, disseminated thrombosis, multi‐organ failure, and death. COVID‐19 pathogenesis is still not fully elucidated, while increasing evidence suggests that disease phenotypes are strongly related to the virus‐induced immune system's dysregulation. Indeed, when the virus‐host cross talk is out of control, the occurrence of an aberrant systemic inflammatory reaction, named “cytokine storm,” leads to a detrimental impairment of the adaptive immune response. Dendritic cells (DCs) are the most potent antigen‐presenting cells able to support innate immune and promote adaptive responses. Besides, DCs play a key role in the anti‐viral defense. The aim of this review is to focus on DC involvement in SARS‐CoV‐2 infection to better understand pathogenesis and clinical behavior of COVID‐19 and explore potential implications for immune‐based therapy strategies.

Published
2021

21. Dendritic Cells Are the Intriguing Players in the Puzzle of Idiopathic Pulmonary Fibrosis Pathogenesis

Author

Ludovica Capitelli, Serena Zanotta, Domenico Galati, Marialuisa Bocchino, Bocchino, M., Zanotta, S., Capitelli, L., and Galati, D.

Subjects
0301 basic medicine, dendritic cell, Mini Review, medicine.medical_treatment, Cell Plasticity, Immunology, 03 medical and health sciences, Idiopathic pulmonary fibrosis, Antineoplastic Agents, Immunological, 0302 clinical medicine, Immune system, Fibrosis, Neoplasms, medicine, Humans, Immunology and Allergy, cancer, Lung, medicine.diagnostic_test, idiopathic pulmonary fibrosi, business.industry, Interstitial lung disease, Cell Differentiation, Dendritic Cells, Immunotherapy, RC581-607, respiratory system, idiopathic pulmonary fibrosis, medicine.disease, Acquired immune system, immunity, respiratory tract diseases, 030104 developmental biology, Bronchoalveolar lavage, medicine.anatomical_structure, Cellular Microenvironment, Disease Susceptibility, immunotherapy, Immunologic diseases. Allergy, business, Biomarkers, 030215 immunology
Abstract

Idiopathic pulmonary fibrosis (IPF) is the most devastating progressive interstitial lung disease that remains refractory to treatment. Pathogenesis of IPF relies on the aberrant cross-talk between injured alveolar cells and myofibroblasts, which ultimately leads to an aberrant fibrous reaction. The contribution of the immune system to IPF remains not fully explored. Recent evidence suggests that both innate and adaptive immune responses may participate in the fibrotic process. Dendritic cells (DCs) are the most potent professional antigen-presenting cells that bridge innate and adaptive immunity. Also, they exert a crucial role in the immune surveillance of the lung, where they are strategically placed in the airway epithelium and interstitium. Immature DCs accumulate in the IPF lung close to areas of epithelial hyperplasia and fibrosis. Conversely, mature DCs are concentrated in well-organized lymphoid follicles along with T and B cells and bronchoalveolar lavage of IPF patients. We have recently shown that all sub-types of peripheral blood DCs (including conventional and plasmacytoid DCs) are severely depleted in therapy naïve IPF patients. Also, the low frequency of conventional CD1c+DCs is predictive of a worse prognosis. The purpose of this mini-review is to focus on the main evidence on DC involvement in IPF pathogenesis. Unanswered questions and opportunities for future research ranging from a better understanding of their contribution to diagnosis and prognosis to personalized DC-based therapies will be explored.

Published
2021

22. Liquid biopsy is a promising tool for genetic testing in idiopathic pulmonary fibrosis

Author

Roberta Sgariglia, Mario Galgani, Ludovica Capitelli, Pierlorenzo Pallante, Alessandro Sanduzzi Zamparelli, Umberto Malapelle, Marialuisa Bocchino, Gaetano Rea, Erica Piemonte, Domenico Galati, Mariantonia Nacchio, Serena Zanotta, Pallante, P., Malapelle, U., Nacchio, M., Sgariglia, R., Galati, D., Capitelli, L., Zanotta, S., Galgani, M., Piemonte, E., Sanduzzi Zamparelli, A., Rea, G., and Bocchino, M.

Subjects
Medicine (General), medicine.medical_specialty, Clinical Biochemistry, Single-nucleotide polymorphism, Gastroenterology, MUC5B, Article, 03 medical and health sciences, Idiopathic pulmonary fibrosis, Cell-free DNA, R5-920, 0302 clinical medicine, Genetic, Polymorphism (computer science), Internal medicine, medicine, genetics, Liquid biopsy, Genetic testing, Lung, Idiopathic pulmonary fibrosi, medicine.diagnostic_test, business.industry, respiratory system, medicine.disease, idiopathic pulmonary fibrosis, respiratory tract diseases, genomic DNA, medicine.anatomical_structure, 030228 respiratory system, Cell-free fetal DNA, 030220 oncology & carcinogenesis, business
Abstract

Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age- and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease.

Published
2021

23. Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction

Author

Antonello D'Andrea, Simona Sperlongano, Patrizio Lancellotti, Serena Zanotta, Marialuisa Bocchino, Giacomo Ghinassi, Giorgio Emanuele Polistina, Carmine Nicoletta, Domenico Galati, Angelo Canora, Alessandro Sanduzzi Zamparelli, Maurizio Galderisi, D'Andrea, Antonello, Canora, Angelo, Sperlongano, Simona, Galati, Domenico, Zanotta, Serena, Polistina, Giorgio Emanuele, Nicoletta, Carmine, Ghinassi, Giacomo, Galderisi, Maurizio, Zamparelli, Alessandro Sanduzzi, Lancellotti, Patrizio, Bocchino, Marialuisa, D'Andrea, A., Canora, A., Sperlongano, S., Galati, D., Zanotta, S., Polistina, G. E., Nicoletta, C., Ghinassi, G., Galderisi, M., Zamparelli, A. S., Lancellotti, P., and Bocchino, M.

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Diastolic function, Systole, Diastole, 030204 cardiovascular system & hematology, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Echocardiography, Stre, medicine.artery, Internal medicine, Stress Echocardiography, Humans, Medicine, Exertion, Subclinical infection, lcsh:RC705-779, Sleep Apnea, Obstructive, Ejection fraction, Ventricular Remodeling, business.industry, 2D speckle tracking echocardiography, Stroke Volume, lcsh:Diseases of the respiratory system, Middle Aged, Hypoxia (medical), medicine.disease, Myocardial Contraction, Obstructive sleep apnea, Oxidative burst, 030228 respiratory system, Case-Control Studies, Pulmonary artery, Cardiology, Exercise echocardiography, Female, medicine.symptom, Case-Control Studie, business, Echocardiography, Stress, Research Article, Human
Abstract

BackgroundHypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset.MethodsConventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry.ResultsDespite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (− 13.4 ± 3.8 vs − 18.4 ± 3.3 in controls,P P P P r = − 0.50,P P = 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction.ConclusionsEvaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.

Published
2020
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24. Circulating dendritic cells are severely decreased in idiopathic pulmonary fibrosis with a potential value for prognosis prediction

Author

Ludovica Capitelli, Domenico Galati, Antonietta Coppola, Marialuisa Bocchino, Giorgio Emanuele Polistina, Serena Zanotta, Galati, D., Zanotta, S., Polistina, G. E., Coppola, A., Capitelli, L., and Bocchino, M.

Subjects
Male, 0301 basic medicine, Immunology, Flow cytometry, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, Interleukin 6, Cytokine, Aged, chemistry.chemical_classification, Reactive oxygen species, Lung, Idiopathic pulmonary fibrosi, biology, medicine.diagnostic_test, business.industry, Interleukin-6, Interleukin, Biomarker, Dendritic Cells, Middle Aged, Prognosis, medicine.disease, Idiopathic Pulmonary Fibrosis, Oxidative burst, Respiratory burst, Peripheral, 030104 developmental biology, medicine.anatomical_structure, chemistry, biology.protein, Cytokines, Female, business, Biomarkers, Dendritic cell, Human, 030215 immunology
Abstract

Dendritic cells (DCs) accumulate in the lung of patients affected by idiopathic pulmonary fibrosis (IPF). We measured the frequencies of circulating conventional CD1c + and CD141+ cells (namely, cDC2 and cDC1) and of plasmacytoid CD303+ DCs in a cohort of 60 therapy naive IPF patients by flow cytometry. Peripheral levels of reactive oxygen species (ROS) and of pro-inflammatory and Th1/Th2 polarizing cytokines were also analyzed. All blood DC subtypes were significantly reduced in IPF patients in comparison to age- and sex-matched controls, while ROS and interleukin (IL-6) levels were augmented. IL-6 expression increased along with disease severity, according to the gender-age-physiology index, and correlated with the frequency of cDC2. IL-6 and cDC2 were not influenced by anti-fibrotic therapies but were associated with a reduced survival, the latter being an independent predictive biomarker of worse prognosis. Deciphering the role of DCs in IPF might provide information on disease pathogenesis and clinical behavior.

Published
2020

25. Housing-Related Subjective Well-Being in Turin (Italy) and Havana (Cuba): Dimensions and Prediction

Author

Michele Roccato, María Victoria Zardoya Loureda, Federica Caffaro, Dario Galati, Caffaro, F., Galati, D., Zardoya Loureda, M. V., and Roccato, M.

Subjects
Emotion, Housing-related subjective well-being, Apartment, 05 social sciences, Housing, Subjective well-being, Housing-related subjective well-being, Housing satisfaction, Italy, Cuba, 0211 other engineering and technologies, Cuba, 021107 urban & regional planning, 02 engineering and technology, Negative association, Housing satisfaction, Subjective well-being, Italy, Per capita, Housing, 0501 psychology and cognitive sciences, Residence, Life-span and Life-course Studies, 050104 developmental & child psychology, Quality of Life Research, Demography
Abstract

In the present study, we conceptualized housing-related subjective well-being (HRSWB) as a three-dimensional construct, defined by positive and negative emotions related to housing and housing satisfaction. Moreover, we predicted the construct via a mediated model, with the objective characteristics of the household as exogenous variables and its subjective evaluation as a mediator. A survey performed on 409 participants (285 residents in Torino, Italy, women = 52.3%, M age = 42.81, SD = 12.73, and 124 residents in Havana, Cuba, women = 58.1%, M age = 40.48, SD = 19.21) showed that fewer square meters per capita and living in an apartment had a negative association with perceived housing quality, which in turn had a positive association with HRSWB. Home ownership was not associated with HRSWB. The model was invariant across genders, age classes, and cities of residence. Possible developments and limitations of this research are discussed.

Published
2018

26. Severe depletion of peripheral blood dendritic cell subsets in obstructive sleep apnea patients: A new link with cancer?

Author

Angelo Canora, Emanuele Ciasullo, Carmine Nicoletta, Marialuisa Bocchino, Giorgio Emanuele Polistina, Giacomo Ghinassi, Serena Zanotta, Domenico Galati, Galati, D., Zanotta, S., Canora, A., Polistina, G. E., Nicoletta, C., Ghinassi, G., Ciasullo, E., and Bocchino, M.

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, Myeloid, Immunology, Inflammation, Comorbidity, Biochemistry, Interferon-gamma, chemistry.chemical_compound, Immune system, Neoplasms, medicine, Humans, Immunology and Allergy, Flow cytometry, Molecular Biology, Cancer, Aged, Respiratory Burst, Sleep Apnea, Obstructive, Interleukin-6, Tumor Necrosis Factor-alpha, business.industry, Interleukin, Dendritic Cells, Hematology, Dendritic cell, Middle Aged, medicine.disease, Obstructive sleep apnea, Oxidative burst, Interleukin-10, Up-Regulation, Vascular endothelial growth factor, medicine.anatomical_structure, chemistry, Cytokines, Interleukin-2, Female, Tumor necrosis factor alpha, Interleukin-4, medicine.symptom, business
Abstract

Recent evidence suggests that alterations of the immune responses are associated with the inflammatory nature of obstructive sleep apnea (OSA) and of its related co-morbidities. In this scenario, we asked whether circulating dendritic cell (DC) subsets may be possible players as their role has not yet been detailed. The frequency distribution of peripheral blood myeloid (mDC1 and mDC2) and plasmacytoid (p) DCs was investigated by mean of multi-parametric flow cytometry in 45 OSA patients (mean age: 53 yrs; M = 29) at the time of the first diagnosis and compared to 30 age- and sex-matched healthy controls. Oxidative burst (OB) and serum levels of tumor necrosis factor (TNF)-α, (interleukin) (IL)-6, interferon (INF)-γ, IL-2, IL-4, IL-10 and vascular endothelial growth factor (VEGF) were also analyzed. All subsets of circulating DCs were significantly depleted in OSA patients as compared to healthy subjects (p < 0.01, in all instances), with mDC2 and pDC subtypes being more severely compromised. These findings were co-existing with higher levels of OB along with an increased expression of IL-6, IL-10, TNF-α, IFN-γ, and VEGF (p < 0.005 in all instances). In particular, IL6 levels were significantly higher (p = 0.013) in severe OSA patients (apnea/hypopnea index >30) and were inversely correlated with both mDC2 (r = −0.802, p < 0.007) and pDC (r = −0.317, p = 0.04) subsets. We first provide evidence for a constitutive reduction of all circulating DC subsets in OSA patients. Perturbation of DCs coexists with an inflammatory milieu and is negatively correlated with the expression of IL-6, which is actually recognized as a pivotal inhibitor of DC maturation. Future studies exploring the contribution of DCs in the pathogenesis of OSA and of its complications should be encouraged.

Published
2020
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27. Peripheral depletion of NK cells and imbalance of the Treg/Th17 axis in idiopathic pulmonary fibrosis patients

Author

Maria Napolitano, Gaetano Cicchitto, Alessandro Sanduzzi, Domenico Galati, Anna Agnese Stanziola, Marina De Martino, Gaetano Rea, Dario Bruzzese, Annamaria Trotta, Marialuisa Bocchino, Galati, D., De Martino, M., Trotta, A., Rea, G., Bruzzese, D., Cicchitto, G., Stanziola, A. A., Napolitano, M., Sanduzzi, A., and Bocchino, M.

Subjects
Male, CD3 Complex, T cell, Immunology, chemical and pharmacologic phenomena, Inflammation, CD8-Positive T-Lymphocytes, Biology, Biochemistry, T-Lymphocytes, Regulatory, Lymphocyte Depletion, Interleukin 21, Idiopathic pulmonary fibrosis, Immune system, Transforming Growth Factor beta, medicine, Humans, Immunology and Allergy, NK cell, Flow cytometry, Molecular Biology, Aged, Autoimmune disease, Th17 cell, Interleukin-17, Idiopathic Pulmonary Fibrosi, Interleukin-2 Receptor alpha Subunit, Interleukin, Forkhead Transcription Factors, Hematology, CD8-Positive T-Lymphocyte, Forkhead Transcription Factor, Middle Aged, medicine.disease, Natural Killer T-Cell, Idiopathic Pulmonary Fibrosis, CD4 Lymphocyte Count, Killer Cells, Natural, medicine.anatomical_structure, IPF, Interleukin 12, Natural Killer T-Cells, Th17 Cells, Female, medicine.symptom, Regulatory T cell, Human
Abstract

The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed. © 2014 Elsevier Ltd.

Published
2014

28. Distinct pathways of neural coupling for different basic emotions

Author

Elena Rognoni, Daniela Perani, Dario Galati, Riccardo Cafiero, Tommaso Costa, Marco Tettamanti, Tettamanti, M, Rognoni, E, Cafiero, R, Costa, T, Galati, D, Perani, D, and Perani, DANIELA FELICITA L.

Subjects
Adult, Cognitive Neuroscience, Emotion classification, media_common.quotation_subject, Emotions, Amygdala, Young Adult, Neural Pathways, medicine, Biological neural network, Humans, Effective connectivity, media_common, Emotional Intelligence, Emotion, DCM, Brain Mapping, Functional integration (neurobiology), Brain, Cognition, Disgust, Sadness, Visual cortex, medicine.anatomical_structure, Neurology, FMRI, Female, Nerve Net, Psychology, Cognitive psychology
Abstract

Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience.

Published
2012

29. Usefulness of IFN-gamma release assays in clinical management of difficult TB cases: Evidence from clinical practice

Author

Giuseppe Signoriello, Marialuisa Bocchino, P. Giacomelli, Barbara Bellofiore, Aniello Russo, A. Sanduzzi, Domenico Galati, Alessandro Matarese, Bocchino, M., Matarese, A, Bellofiore, B, Giacomelli, P, Russo, A, Signoriello, Giuseppe, Galati, D, Sanduzzi, A., Bocchino, Marialuisa, and Signoriello, G

Subjects
tuberculin test, Tuberculosis, business.industry, Immunology, lcsh:R, lcsh:Medicine, medicine.disease, bacterial infections and mycoses, Clinical Practice, Extra pulmonary tuberculosis, tuberculosis, Gamma interferon, Immunology and Allergy, Medicine, gamma interferon, business, Tuberculin test, Ifn gamma
Abstract

Performance of T-SPOT.TB™ (TS-TB) and QuantiFERON TB Gold-In tube (QFT-IT) assays was evaluated for detection of M. tuberculosis (Mtb) infection in patients with suspected extra-pulmonary or smear-negative pulmonary tuberculosis (TB) in a low prevalence country. Twenty-one out of 35 patients were affected by active TB. Mtb culture isolation was achieved in 76% of cases. Tuberculin skin testing (TST), TS-TB, and QFT-IT yielded a positive result in 67%, 95% and 81% of cases, respectively. Agreement of interferon-γ release assays and TST was 70% (κ=0.18 for TS-TB; κ=0.46 for QFT-IT). Increased sensitivity of blood assays (>80%) improved diagnostic evaluation of difficult TB cases. Copyright © by BIOLIFE, s.a.s.

Published
2010

30. Analysis of Mycobacterium tuberculosis-Specific CD8 T-Cells in Patients with Active Tuberculosis and in Individuals with Latent Infection

Author

Alfredo Salerno, Alessandro Sanduzzi, Domenico Galati, Alessandro Matarese, Lucina Titone, Marialuisa Bocchino, Michèl R. Klein, Francesco Dieli, Tom H. M. Ottenhoff, Giuseppe Gelsomino, Paola Di Carlo, Jan Nouta, Nadia Caccamo, Serena Meraviglia, Giuliana Guggino, Caccamo, N, Guggino, G, Meraviglia, S, Gelsomino, G, Di Carlo, P, Titone Lanza Di Scalea, L, Bocchino, M, Galati, D, Matarese, A, Nouta, J, Klein, MR, Salerno, A, Sanduzzi, A, Dieli, F, Ottenhoff, TH, Titone, L, Bocchino, Marialuisa, Matarese, Alessandro, Klein, Mr, SANDUZZI ZAMPARELLI, Alessandro, and Ottenhoff, Th

Subjects
Male, Epitopes, T-Lymphocyte, lcsh:Medicine, CD8-Positive T-Lymphocytes, Epitope, Diagnostic Radiology, Infectious Diseases/Bacterial Infections, Spectrum Analysis Techniques, Cellular types, Cytotoxic T cell, lcsh:Science, Image Cytometry, education.field_of_study, Multidisciplinary, biology, Radiology and Imaging, Immune cells, Infection Imaging, Middle Aged, Flow Cytometry, Actinobacteria, Phenotype, Spectrophotometry, Cytokines, White blood cells, Female, Cytophotometry, Research Article, medicine.drug, Interleukin 2, Cell biology, Blood cells, Tuberculosis, Imaging Techniques, Immunology, Population, T cells, Cytotoxic T cells, Research and Analysis Methods, Mycobacterium tuberculosis, Diagnostic Medicine, Immunology/Immunity to Infections, HLA-A2 Antigen, medicine, Humans, education, Medicine and health sciences, HLA-A Antigens, Bacteria, Fluorimetry, lcsh:R, Organisms, Biology and Life Sciences, biology.organism_classification, medicine.disease, Virology, Retraction, Animal cells, Immunology/Immune Response, Mycobacterium tuberculosis, CD8 T cells, Tuberculosis, Latent Infection, lcsh:Q, CD8, Mycobacterium
Abstract

CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).

Published
2009

31. Induced sputum as a tool for early detection of airway inflammation in connective diseases-related lung involvement

Author

Alessandro Vatrella, Raffaele Scarpa, Marialuisa Bocchino, Girolamo Pelaia, Sergio Spina, Mario Cazzola, Francesco Perna, Alessandro Sanduzzi, Domenico Galati, Vatrella, A, Bocchino, Marialuisa, Perna, Francesco, Scarpa, R, Galati, D, Spina, S, Pelaia, G, Cazzola, M, and SANDUZZI ZAMPARELLI, Alessandro

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, High-resolution computed tomography, Pathology, medicine.medical_specialty, Neutrophils, Settore MED/10 - Malattie dell'Apparato Respiratorio, Vital Capacity, CD4-CD8 Ratio, Cell Count, Bronchoalveolar Lavage, Specimen Handling, Lung Disorder, Arthritis, Rheumatoid, Forced Expiratory Volume, airway inflammation, connective tissue diseases, induced sputum, neutrophils, medicine, Humans, Induced sputum, Lung volumes, Connective tissue diseases, Lung, Scleroderma, Systemic, medicine.diagnostic_test, business.industry, Macrophages, Respiratory disease, Total Lung Capacity, Sputum, Middle Aged, respiratory system, medicine.disease, Connective tissue disease, respiratory tract diseases, medicine.anatomical_structure, Bronchoalveolar lavage, Early Diagnosis, Case-Control Studies, Female, medicine.symptom, business, Lung Diseases, Interstitial, Bronchoalveolar Lavage Fluid, Airway inflammation
Abstract

SummaryBackgroundInduced sputum (IS) sampling is a safe and validated approach to study bronchial inflammation in chronic obstructive lung diseases. Although promising results have also been reported in various diffuse interstitial lung disorders, the potential use of IS in the assessment of connective tissue diseases (CTD)-related lung involvement has not yet been investigated.Aim of the studyTo evaluate the clinical usefulness of IS in the early management of patients suffering from rheumatoid arthritis (RA) and systemic sclerosis (SSc) at the onset of respiratory symptoms.Patients and methodsThe study population included 19 patients (RA=12; SSc=7) and 14 age- and sex-matched healthy volunteers. Lung function testing, high resolution computed tomography (HRCT) of the thorax and IS collection were performed in all cases. Broncho-alveolar lavage (BAL) was obtained in selected patients.ResultsIS samples from patients contained a significantly higher percentage of neutrophils and a lower percentage of macrophages compared to healthy subjects (p=0.002 and 0.001, respectively), while the total cell number showed no differences. In addition, sputa yielded both higher cell counts and higher neutrophils than BAL samples (p=0.02 in all instances). No correlations were found between IS findings and lung function parameters, HRCT and BAL findings.ConclusionsThis is the first study investigating the inflammatory cell pattern in IS from CTD patients with early clinical evidence of lung involvement. Future studies are needed to determine whether the assessment of airway inflammation adds significant information that may result in a relevant improvement of disease management.

Published
2007

32. The effects of religious involvement on short-term psychological reactions to the death of Pope John Paul II: A study on an italian sample

Author

Igor Sotgiu, Dario Galati, Susanna Schmidt, Antonietta Curci, N Businaro, Carla Tinti, Schmidt, S, Sotgiu, I, Tinti, C, Curci, A, Businaro, N, and Galati, D

Subjects
Settore M-PSI/01 - Psicologia Generale, FLASHBULB MEMORIES, Social Psychology, Recall, Cognitive and emotional impact, business.industry, Pope john paul ii, Religious involvement, cognitive and emotional impact, public event, Pope John Paul II, surprise-expectedness, mass media, Cognition, Sample (statistics), Term (time), Public event, EMOTIONS, Surprise-expectedness, Immediate memory, M-PSI/01 - PSICOLOGIA GENERALE, Psychology, business, Social psychology, Mass media, Questionnaire study
Abstract

The short-term psychological reactions to the death of Pope John Paul II were investigated. Between 1 to 6 days after this event, 526 Catholic and atheist Italian adults took part in a questionnaire study. Participants were asked to report the personal circumstances in which they first learned about the Pope's death, their emotional reactions, and their appraisal of the event's importance and consequentiality. Other questions assessed immediate memory for the original event, surprise-expectedness, exposure to mass media, and religious involvement. Results showed that the news of the Pope's death, although widely expected, had a strong cognitive and emotional impact. Almost all the participants were able to recall the personal circumstances in which they heard the news. A positive relation was observed between the degree of religious involvement and appraisal of importance and consequentiality, intensity of emotion, memory for event-related details, and frequency of exposure to mass media. Effects related to the age of the participants were also found. © Society for Personality Research (Inc.).

Published
2007

33. Sulodexide versus calcium heparin in the medium-term treatment of deep vein thrombosis of the lower limbs

Author

Antonio Pinto, Salvatore Corrao, Domenico Galati, Sabrina Arnone, Anna Licata, Gaspare Parrinello, Tiziana Maniscalchi, Giuseppe Licata, Pinto, A, Corrao, S, Galati, D, Arnone, S, Licata, A, Parrinello, G, Maniscalchi, T, and Licata, G

Subjects
Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, medicine.drug_class, Deep vein, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Humans, Medicine, 030212 general & internal medicine, Thrombus, Aged, Glycosaminoglycans, medicine.diagnostic_test, Heparin, business.industry, Anticoagulant, Middle Aged, Thrombophlebitis, medicine.disease, Thrombosis, Sulodexide, Surgery, medicine.anatomical_structure, Tolerability, Anesthesia, Settore BIO/14 - Farmacologia, Female, Adult Aged Female Fibrinolytic Agents/administration & dosage Fibrinolytic Agents/therapeutic use* Glycosaminoglycans/administration & dosage Glycosaminoglycans/therapeutic use* Heparin/therapeutic use* Humans Male Middle Aged Thrombophlebitis/drug therapy, Cardiology and Cardiovascular Medicine, business, medicine.drug, Partial thromboplastin time
Abstract

Thirty adult patients with distal, monolateral deep vein thrombosis of the lower limbs were randomly treated for sixty days either with subcutaneous Ca-Heparin or with Sulodexide, administered IM for ten days and orally for fifty days. The thrombus accretion above the knee, the venous pressures of the affected leg, the clinical sympto matology, and some laboratory coagulative tests were monitored throughout the admin istration period. Local tolerability of the two treatments was also evaluated.The two applied treatments evidenced a net antithrombotic activity, preventing thrombus accretion above the knee, improving with the same efficacy the venous pressures in the affected legs, and similarly reducing clinical symptoms, with a quick and statistically significant trend toward normalization. Blood fibrinogen was significantly lowered by both drugs, while only Ca-heparin yielded a prolongation of activated partial thromboplastin time. Local tolerability of treatments was better for the mainly oral Sulodexide administrations, while subcutaneous Ca-heparin often induced small, though transient, hematomas.

34. Evaluation of regional haemodynamics and alterations of vascular wall of the lower limbs in hypertensive subjects

Author

G. Licata, Rosario Scaglione, Salvatore Paterna, S. Arnone, Antonio Pinto, Gaspare Parrinello, Domenico Galati, Pinto,A, Scaglione,R, Galati,D, Paterna,S, Parrinello,G, arnone,S, and Licata,G

Subjects
Adult, Male, Duplex ultrasonography, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Hemodynamics, Essential Hypertension, Arterial blood flow of the lower limbs, medial-intima thickening, Hyperaemia, Internal medicine, medicine.artery, medicine, Plethysmograph, Humans, Knee, Aged, Ultrasonography, Leg, business.industry, Blood flow, Arteries, Middle Aged, Settore MED/11 - Malattie Dell'Apparato Cardiovascolare, Popliteal artery, Surgery, Mean blood pressure, medicine.anatomical_structure, Regional Blood Flow, Hypertension, Cardiology, Female, Vascular Resistance, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Tunica Intima, Tunica Media, Artery
Abstract

This study was designed to analyse the relationship between arterial hypertension and changes in arterial blood flow and vascular wall damage of the lower limbs in hypertensive patients with various degrees of hypertension. Six hundred and fifty-four hypertensive patients (421 males and 233 females) aged 35 to 70 years and 88 healthy subjects (63 males and 25 females) aged 39 to 60 years were studied. Strain-gauge plethysmography of the lower limbs was used to calculate arterial calf blood flow (RF), arterial calf blood flow after post-ischaemic hyperaemia (PF), basal and minimal vascular resistances (BVR and MVR), time to reach peak flow (tPF), time until 50% reduction of peak flow (tT1/2) and total recovery time (tT). In 108 (67 males and 41 females) of the hypertensive patients, a morphological study by echo-Doppler duplex scanning of the popliteal artery was performed to measure medial-intimal thickening and popliteal lumen diameter. Our results indicate that regional haemodynamics of the lower limbs worsened in hypertensives in comparison with control subjects. In addition, the change in peripheral haemodynamics was related to the degree of hypertension. Moreover, medial--intimal thickening was significantly (P < 0.05) higher in severe hypertensives than mild hypertensives. Popliteal lumen diameter was significantly (P < 0.05) lower in severe hypertensives than moderate and mild hypertensives. In all these subjects mean blood pressure was correlated directly (r = 0.31; P < 0.001) with medial-intimal thickening and inversely (r = -0.37; P < 0.001) with popliteal lumen diameter. Multiple regression analysis indicated that mean blood pressure, age and serum cholesterol were independently correlated to medial-intimal thickening. This relationship was not influenced by the diabetic patients and smokers among the groups. Our results indicate that hypertension impairs peripheral flow and encourages the development of medial-intimal thickening.

35. Enhancing Dendritic Cell Cancer Vaccination: The Synergy of Immune Checkpoint Inhibitors in Combined Therapies.

Author

Zanotta S, Galati D, De Filippi R, and Pinto A

Subjects
Humans, Combined Modality Therapy, Animals, Immunotherapy methods, Vaccination methods, Dendritic Cells immunology, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Cancer Vaccines immunology, Cancer Vaccines therapeutic use, Neoplasms therapy, Neoplasms immunology, Neoplasms drug therapy
Abstract

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.

Published
2024
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36. The Dysregulation of the Monocyte-Dendritic Cell Interplay Is Associated with In-Hospital Mortality in COVID-19 Pneumonia.

Author

Galati D, Mallardo D, Nicastro C, Zanotta S, Capitelli L, Lombardi C, Baino B, Cavalcanti E, Sale S, Labonia F, Boenzi R, Atripaldi L, Ascierto PA, and Bocchino M

Abstract

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F; mean age ± SD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169 + monocytes, conventional CD1c + and CD141 + (namely cDC2 and cDC1), and plasmacytoid CD303 + DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory-related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls ( p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients ( p < 0.0001). COVID-19 cases with absolute counts of CD169 + monocytes above the median value of 114.68/μL had significantly higher in-hospital mortality (HR 4.96; 95% CI: 1.42-17.27; p = 0.02). Interleukin (IL)-6 concentrations were significantly increased in COVID-19 patients ( p < 0.0001 vs. controls), and negatively correlated with the absolute counts of circulating CD1c + cDC2 (r = -0.29, p = 0.034) and CD303 + pDC (r = -0.29, p = 0.036) subsets. Viral genes were upregulated in patients with worse outcomes along with inflammatory mediators such as interleukin (IL)-1 beta, tumor necrosis-α (TNF-α) and the anticoagulant protein (PROS1). Conversely, surviving patients had upregulated genes related to inflammatory and anti-viral-related pathways along with the T cell membrane molecule CD4. Conclusions: Our results suggest that the dysregulated interplay between the different components of the MPS along with the imbalance between viral gene expression and host anti-viral immunity negatively impacts COVID-19 outcomes. Although the clinical scenario of COVID-19 has changed over time, a deepening of its pathogenesis remains a priority in clinical and experimental research.

Published
2024
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37. Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123.

Author

Zanotta S, Galati D, De Filippi R, and Pinto A

Subjects
Humans, Dendritic Cells, Neoplasm Recurrence, Local pathology, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Stem Cell Transplantation, Hematologic Neoplasms drug therapy, Hematologic Neoplasms pathology, Interleukin-3 Receptor alpha Subunit drug effects, Myeloproliferative Disorders drug therapy, Myeloproliferative Disorders pathology
Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. The recognition of BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift toward CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combinations of treatments with other anti-leukemic drugs. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy.

Published
2024
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38. Potential clinical implications of CD4 + CD26 high T cells for nivolumab treated melanoma patients.

Author

Galati D, Zanotta S, Capone M, Madonna G, Mallardo D, Romanelli M, Simeone E, Festino L, Sparano F, Azzaro R, De Filippi R, Pinto A, Paulos CM, and Ascierto PA

Subjects
Humans, T-Lymphocytes, Dipeptidyl Peptidase 4 therapeutic use, Progression-Free Survival, Nivolumab pharmacology, Nivolumab therapeutic use, Melanoma pathology
Abstract

Background: Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients' outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe off-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will benefit from anti-PD-1 treatment avoiding unwanted side effects. However, the strength of CD26 expression on CD4 + T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies., Methods: The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multi-parametric flow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4 + CD26 high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4 + CD26 high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients., Results: Circulating CD4 + CD26 high T cells were significantly reduced in melanoma patients compared to healthy subjects (p = 0.001). In addition, a significant association was observed between a low baseline percentage of CD4 + CD26 high T cells (< 7.3%) and clinical outcomes, measured as overall survival (p = 0.010) and progression-free survival (p = 0.014). Moreover, patients with clinical benefit from nivolumab therapy had significantly higher frequencies of circulating CD4 + CD26 high T cells than patients with non-clinical benefit (p = 0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4 + CD26 high T cells was correlated with Disease Control Rate (p = 0.014) and best Overall Response Rate (p = 0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4 + CD26 high T cells were significantly higher in comparison with the frequencies measured at W0 (p < 0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects., Conclusions: Our study firstly demonstrates that peripheral blood circulating CD4 + CD26 high T lymphocytes represent potential biomarkers whose perturbations are associated with reduced survival and worse clinical outcomes in melanoma patients., (© 2023. The Author(s).)

Published
2023
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39. Dendritic Cell and Cancer Therapy.

Author

Galati D and Zanotta S

Subjects
Humans, Adaptive Immunity, Immunity, Innate, Dendritic Cells, Neoplasms
Abstract

Dendritic cells (DCs) are acknowledged as the most potent professional antigen-presenting cells (APCs), able to induce adaptive immunity and support the innate immune response [...]., Competing Interests: The authors declare no conflicts of interest.

Published
2023
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40. Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis.

Author

Mallardo D, Giannarelli D, Vitale MG, Galati D, Trillò G, Esposito A, Isgrò MA, D'Angelo G, Festino L, Vanella V, Trojaniello C, White A, De Cristofaro T, Bailey M, Pignata S, Caracò C, Petrillo A, Muto P, Maiolino P, Budillon A, Warren S, Cavalcanti E, and Ascierto PA

Subjects
Humans, Nivolumab therapeutic use, Retrospective Studies, Genetic Profile, Antibodies, Monoclonal therapeutic use, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, Neoplasms, Second Primary chemically induced
Abstract

Background: Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes., Methods: In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient's genetic profile plays a role in this association., Results: We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival. Moreover, patients who achieved a clinical or partial response tended to have higher levels of nivolumab than those who reached stable disease or had disease progression. However, the difference was not statistically significant. In particular, patients who reached a clinical response had a significantly higher concentration of nivolumab and presented a distinct genetic signature, with more marked activation of ICOS and other genes involved in effector T-cells mediated proinflammatory pathways., Conclusions: In conclusion, these preliminary results show that in patients with MM, nivolumab concentration correlates with clinical outcomes and is associated with an increased expression of ICOS and other genes involved in the activation of T effectors cells., Competing Interests: Competing interests: PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. SW is employee and stockholder in NanoString Technologies. All other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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41. Gender Differences in the Associations Between Perceived Parenting Styles and Young Adults' Cyber Dating Abuse.

Author

Paleari FG, Celsi L, Galati D, and Pivetti M

Abstract

Existing literature indicates that parenting styles affect the development of cyber aggression in offspring differently, depending on the gender of children. The present study investigates whether mothers' and fathers' parenting styles show similar gender differences in their associations with a new form of dating violence, i.e., cyber dating abuse (CDA). The limited evidence on the issue focuses on the relation that each parenting style has with CDA perpetration, without considering CDA victimization and the joint effects of fathers' and mothers' parenting styles. The present study contributes to the research on gender differences in parenting by examining whether young adults' perceptions of maternal and paternal parenting styles during childhood were independently and/or jointly related to their perpetrated and suffered CDA and whether these relations differed across young adults' gender. In total, 351 young adults (50.7% men), age between 18 and 35 years and having a romantic relationship, completed online self-reports of the variables of interest that include a bidimensional measure of perpetrated/suffered CDA that assess aggression and control. Results showed that maternal authoritarian parenting was uniquely and positively associated to their children's perpetration and victimization of cyber dating control, whereas maternal permissive parenting was uniquely and positively related to their children's perpetration of cyber dating aggression and victimization of cyber dating control. For daughters, these associations were stronger when the father's style was similar to the mother's one or when a maternal authoritarian style combined with a paternal permissive style, thus indicating that the two parents' parenting styles interact in relating to their daughters' CDA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Paleari, Celsi, Galati and Pivetti.)

Published
2022
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42. Liquid Biopsy Is a Promising Tool for Genetic Testing in Idiopathic Pulmonary Fibrosis.

Author

Pallante P, Malapelle U, Nacchio M, Sgariglia R, Galati D, Capitelli L, Zanotta S, Galgani M, Piemonte E, Sanduzzi Zamparelli A, Rea G, and Bocchino M

Abstract

Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age- and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease.

Published
2021
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43. The subtle interplay between gamma delta T lymphocytes and dendritic cells: is there a role for a therapeutic cancer vaccine in the era of combinatorial strategies?

Author

Galati D, Zanotta S, Bocchino M, De Filippi R, and Pinto A

Subjects
Animals, Cancer Vaccines immunology, Humans, Neoplasms immunology, Receptors, Antigen, T-Cell, gamma-delta metabolism, Cancer Vaccines administration & dosage, Dendritic Cells immunology, Immunity, Innate immunology, Immunotherapy methods, Lymphocyte Activation immunology, Neoplasms therapy, Receptors, Antigen, T-Cell, gamma-delta immunology
Abstract

Human gamma delta (γδ) T cells represent heterogeneous subsets of unconventional lymphocytes with an HLA-unrestricted target cell recognition. γδ T cells display adaptive clonally restricted specificities coupled to a powerful cytotoxic function against transformed/injured cells. Dendritic cells (DCs) are documented to be the most potent professional antigen-presenting cells (APCs) able to induce adaptive immunity and support the innate immune response independently from T cells. Several data show that the cross-talk of γδ T lymphocytes with DCs can play a crucial role in the orchestration of immune response by bridging innate to adaptive immunity. In the last decade, DCs, as well as γδ T cells, have been of increasing clinical interest, especially as monotherapy for cancer immunotherapy, even though with unpredictable results mainly due to immune suppression and/or tumor-immune escape. For these reasons, new vaccine strategies have to be explored to reach cancer immunotherapy's full potential. The effect of DC-based vaccines on γδ T cell is less extensively investigated, and a combinatorial approach using DC-based vaccines with γδ T cells might promote a strong synergy for long-term tumor control and protection against escaping tumor clones. Here, we discuss the therapeutic potential of the interaction between DCs and γδ T cells to improve cancer vaccination. In particular, we describe the most relevant and updated evidence of such combinatorial approaches, including the use of Zoledronate, Interleukin-15, and protamine RNA, also looking towards future strategies such as CAR therapies.

Published
2021
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44. Dendritic Cells Are the Intriguing Players in the Puzzle of Idiopathic Pulmonary Fibrosis Pathogenesis.

Author

Bocchino M, Zanotta S, Capitelli L, and Galati D

Subjects
Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological therapeutic use, Biomarkers, Cell Differentiation immunology, Cell Plasticity immunology, Cellular Microenvironment immunology, Humans, Idiopathic Pulmonary Fibrosis pathology, Immunity, Neoplasms complications, Neoplasms etiology, Neoplasms metabolism, Neoplasms pathology, Dendritic Cells immunology, Dendritic Cells metabolism, Disease Susceptibility immunology, Idiopathic Pulmonary Fibrosis etiology, Idiopathic Pulmonary Fibrosis metabolism
Abstract

Idiopathic pulmonary fibrosis (IPF) is the most devastating progressive interstitial lung disease that remains refractory to treatment. Pathogenesis of IPF relies on the aberrant cross-talk between injured alveolar cells and myofibroblasts, which ultimately leads to an aberrant fibrous reaction. The contribution of the immune system to IPF remains not fully explored. Recent evidence suggests that both innate and adaptive immune responses may participate in the fibrotic process. Dendritic cells (DCs) are the most potent professional antigen-presenting cells that bridge innate and adaptive immunity. Also, they exert a crucial role in the immune surveillance of the lung, where they are strategically placed in the airway epithelium and interstitium. Immature DCs accumulate in the IPF lung close to areas of epithelial hyperplasia and fibrosis. Conversely, mature DCs are concentrated in well-organized lymphoid follicles along with T and B cells and bronchoalveolar lavage of IPF patients. We have recently shown that all sub-types of peripheral blood DCs (including conventional and plasmacytoid DCs) are severely depleted in therapy naïve IPF patients. Also, the low frequency of conventional CD1c + DCs is predictive of a worse prognosis. The purpose of this mini-review is to focus on the main evidence on DC involvement in IPF pathogenesis. Unanswered questions and opportunities for future research ranging from a better understanding of their contribution to diagnosis and prognosis to personalized DC-based therapies will be explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bocchino, Zanotta, Capitelli and Galati.)

Published
2021
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45. Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients.

Author

Capone M, Fratangelo F, Giannarelli D, Sorrentino C, Turiello R, Zanotta S, Galati D, Madonna G, Tuffanelli M, Scarpato L, Grimaldi AM, Esposito A, Azzaro R, Pinto A, Cavalcanti E, Pinto A, Morello S, and Ascierto PA

Subjects
CD8-Positive T-Lymphocytes, Humans, Prognosis, Programmed Cell Death 1 Receptor, Melanoma drug therapy, Nivolumab pharmacology, Nivolumab therapeutic use
Abstract

Background: PD-1 blocking agents, such as nivolumab, have demonstrated clear anti-tumor effects and clinical benefits in a subset of patients with advanced malignancies. Nonetheless, more efforts are needed to identify reliable biomarkers for outcome, to correctly select patients who will benefit from anti-PD-1 treatment. The aim of this study was to investigate the role of peripheral CD8+T cells expressing CD73, involved in the generation of the immune suppressive molecule adenosine, in predicting outcome after nivolumab treatment in advanced melanoma patients., Methods: PBMCs from 100 melanoma patients treated with nivolumab were collected at National Cancer Institute "G. Pascale" of Naples. Frequencies of CD8+ lymphocytes phenotypes were assessed by flow cytometry at baseline before nivolumab treatment, along with clinical characteristics and blood count parameters. Healthy controls (n = 20) were also analysed. Percentages of baseline T cells expressing PD-1 and CD73 were correlated with outcome after nivolumab treatment., Results: Melanoma patients presented a lower frequency of total circulating CD8+ lymphocytes than control subjects (p = 0.008). Patients with low baseline percentage of circulating CD8+PD-1+CD73+ lymphocytes (< 2.3%) had better survival (22.4 months vs 6.9 months, p = 0.001). Patients (39%) with clinical benefit from nivolumab therapy presented a significantly lower frequency of circulating CD8+PD-1+CD73+ lymphocytes than patients who progressed to nivolumab treatment (p = 0.02)., Conclusions: Our observations suggest that baseline CD73 expression on circulating CD8+PD-1+ lymphocytes appear a promising biomarker of response to anti-PD-1 treatment in melanoma patients. Further investigations are needed for validation and for clarifying its role as prognostic or predictive marker.

Published
2020
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46. Empowering dendritic cell cancer vaccination: the role of combinatorial strategies.

Author

Galati D and Zanotta S

Subjects
Adaptive Immunity, Animals, CTLA-4 Antigen immunology, Cancer Vaccines immunology, Dendritic Cells transplantation, Humans, Immunity, Innate, Immunosuppressive Agents pharmacology, Immunotherapy methods, Neoplasms immunology, T-Lymphocytes immunology, Cancer Vaccines pharmacology, Dendritic Cells immunology, Neoplasms therapy, Tumor Microenvironment immunology
Abstract

Dendritic cells (DCs) are bone marrow-derived immune cells that play a crucial role in inducing the adaptive immunity and supporting the innate immune response independently from T cells. In the last decade, DCs have become a hopeful instrument for cancer vaccines that aims at re-educating the immune system, leading to a potent anti-cancer immune response able to overcome the immunosuppressive tumor microenvironment (TME). Although several studies have indicated that DC-based vaccines are feasible and safe, the clinical advantages of DC vaccination as monotherapy for most of the neoplasms remain a distant target. Recently, many reports and clinical trials have widely used innovative combinatorial therapeutic strategies to normalize the immune function in the TME and synergistically enhance DC function. This review will describe the most relevant and updated evidence of the anti-cancer combinatorial approaches to boost the clinical potency of DC-based vaccines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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47. Dendritic cells in hematological malignancies.

Author

Galati D, Corazzelli G, De Filippi R, and Pinto A

Subjects
Animals, B-Lymphocytes immunology, Cell Differentiation, Dendritic Cells cytology, Humans, T-Lymphocytes immunology, Dendritic Cells immunology, Hematologic Neoplasms immunology
Abstract

Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a crucial role in initiating and modulating the adaptive immune response and supporting the innate immune response independently from T cells. While functioning as the most effective antigen-presenting cells within the immune system, DCs can otherwise induce tolerance in central and peripheral lymphoid organs acting therefore as suppressors rather than stimulators of the immune response. Within mechanisms regulating antitumor immunity, DCs can capture antigens from viable or damaged tumor cells and present the processed peptides to T-cells to prompt the generation and maintenance of an effective tumor-specific T-cell response. Upon a complex cross-talk with other cellular components of the tumor microenvironment, DCs can, on the other hand, exert a potent antigen-dependent and -independent tolerogenic function by favoring the process of tumor immune evasion. Due to this dual-role in balancing antitumor immunity and tolerance, possibly linked to distinct developmental stages and functional subsets, several studies have addressed the regulatory significance of DCs in different types of malignancies. This review summarizes the most significant pieces of evidence highlighting the critical relevance of bone marrow-derived DCs within the immune pathways regulating pathogenesis and progression of hemopoietic tumors., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Published
2016
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48. Chibby functions in Xenopus ciliary assembly, embryonic development, and the regulation of gene expression.

Author

Shi J, Zhao Y, Galati D, Winey M, and Klymkowsky MW

Subjects
Animals, Carrier Proteins genetics, Cilia physiology, DNA Primers genetics, Embryonic Development genetics, Immunoblotting, Immunohistochemistry, In Situ Hybridization, Intracellular Signaling Peptides and Proteins, Microscopy, Confocal, Neural Plate metabolism, Nuclear Proteins genetics, Real-Time Polymerase Chain Reaction, Xenopus Proteins genetics, Xenopus laevis metabolism, Carrier Proteins metabolism, Cilia genetics, Embryonic Development physiology, Gene Expression Regulation, Developmental genetics, Gene Expression Regulation, Developmental physiology, Nuclear Proteins metabolism, Xenopus Proteins metabolism, Xenopus laevis embryology
Abstract

Wnt signaling and ciliogenesis are core features of embryonic development in a range of metazoans. Chibby (Cby), a basal-body associated protein, regulates β-catenin-mediated Wnt signaling in the mouse but not Drosophila. Here we present an analysis of Cby's embryonic expression and morphant phenotypes in Xenopus laevis. Cby RNA is supplied maternally, negatively regulated by Snail2 but not Twist1, preferentially expressed in the neuroectoderm, and regulates β-catenin-mediated gene expression. Reducing Cby levels reduced the density of multiciliated cells, the number of basal bodies per multiciliated cell, and the numbers of neural tube primary cilia; it also led to abnormal development of the neural crest, central nervous system, and pronephros, all defects that were rescued by a Cby-GFP chimera. Reduction of Cby led to an increase in Wnt8a and decreases in Gli2, Gli3, and Shh RNA levels. Many, but not all, morphant phenotypes were significantly reversed by the Wnt inhibitor SFRP2. These observations extend our understanding of Cby's role in mediating the network of interactions between ciliogenesis, signaling systems and tissue patterning., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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49. Peripheral depletion of NK cells and imbalance of the Treg/Th17 axis in idiopathic pulmonary fibrosis patients.

Author

Galati D, De Martino M, Trotta A, Rea G, Bruzzese D, Cicchitto G, Stanziola AA, Napolitano M, Sanduzzi A, and Bocchino M

Subjects
Aged, CD3 Complex biosynthesis, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes immunology, Female, Forkhead Transcription Factors biosynthesis, Humans, Idiopathic Pulmonary Fibrosis pathology, Interleukin-17 biosynthesis, Interleukin-17 blood, Interleukin-17 immunology, Interleukin-2 Receptor alpha Subunit biosynthesis, Male, Middle Aged, Natural Killer T-Cells immunology, Transforming Growth Factor beta biosynthesis, Transforming Growth Factor beta blood, Transforming Growth Factor beta immunology, Idiopathic Pulmonary Fibrosis immunology, Killer Cells, Natural immunology, Lymphocyte Depletion, T-Lymphocytes, Regulatory immunology, Th17 Cells immunology
Abstract

The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p<0.001). Conversely, the proportion and absolute number of CD3(+)CD4(+)CD25(high)Foxp-3(+) cells were significantly increased in IPF patients (p=0.000). As in controls, almost the totality of cells (>90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
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50. Limited usefulness of QuantiFERON-TB Gold In-Tube for monitoring anti-tuberculosis therapy.

Author

Bocchino M, Chairadonna P, Matarese A, Bruzzese D, Salvatores M, Tronci M, Moscariello E, Galati D, Alma MG, Sanduzzi A, and Altieri AM

Subjects
Adolescent, Adult, Aged, Ambulatory Care, Female, Humans, Italy, Longitudinal Studies, Male, Middle Aged, Treatment Outcome, Tuberculosis, Pulmonary metabolism, Young Adult, Antitubercular Agents therapeutic use, Drug Monitoring methods, Gold therapeutic use, Interferon-gamma metabolism, Tuberculosis, Pulmonary drug therapy
Abstract

The usefulness of IFN-gamma release assays to monitor the efficacy of anti-tuberculosis (TB) treatment is controversial. Sixty patients affected by culture-confirmed pulmonary TB (M = 36; mean age: 39.2 yr; Italians = 28) were serially tested in a low prevalence setting by means of QuantiFERON-TB GOLD In-Tube (QFT-IT) at baseline and after a successful six-month therapy regimen (T6). A sub-group of 40 cases was also tested at 1 and 3 months. Overall, 88.3% of patients scored a QFT-IT positive result at baseline, with the higher proportion of TB-specific IFN-gamma responses in foreign-born patients (p = 0.04). TB-specific responses were highly variable over time, the within-person variability being correlated with baseline IFN-gamma levels (r = 0.731; p < 0.001). Overall, 61.6% of cases still tested QFT-IT positive at the completion of therapy. Average IFN-gamma levels increased over time, being persistently significantly higher in Italian patients than in foreign-born cases both at baseline (p = 0.03) and at T6 (p = 0.02). Reversion mainly occurred in patients (26.6%) with baseline IFN-gamma levels close to the conventional cut-off value. No indeterminate results were recorded at any study time point. In conclusion, QFT-IT adds no significant information to clinicians for treatment monitoring when applied in routine clinical practice in a low prevalence setting. Kinetics of T cell responses upon TB treatment and reversion (and conversion) thresholds need to be addressed. Diversity of IFN-gamma responses among patients of different geographic origin is an issue to be investigated further.

Published
2010
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