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1. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease.

Author

Maria Wilbe, Sergey V Kozyrev, Fabiana H G Farias, Hanna D Bremer, Anna Hedlund, Gerli R Pielberg, Eija H Seppälä, Ulla Gustafson, Hannes Lohi, Örjan Carlborg, Göran Andersson, Helene Hansson-Hamlin, and Kerstin Lindblad-Toh

Subjects
Genetics, QH426-470
Abstract

The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.

Published
2015
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2. Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study

Author

Arends, S., Treppo, E., Longhino, S., Manfrè, V., Rizzo, M., Baldini, C., Bombardieri, S., Bandeira, M., Silvéiro-António, M., Seror, R., Mariette, X., Nordmark, G., Danda, D., Wiland, P., Gerli, R., Kwok, S.K., Park, S.H., Kvarnstrom, M., Wahren-Herlenius, M., Downie-Doyle, S., Sene, D., Isenberg, D., Valim, V., Devauchelle-Pensec, V., Saraux, A., Morel, J., Morcillo, C., Díaz Cuiza, P.E., Herrera, B.E., González-de-Paz, L., Sisó-Almirall, A., Brito-Zerón, Pilar, Flores-Chávez, Alejandra, Horváth, Ildiko Fanny, Rasmussen, Astrid, Li, Xiaomei, Olsson, Peter, Vissink, Arjan, Priori, Roberta, Armagan, Berkan, Hernandez-Molina, Gabriela, Praprotnik, Sonja, Quartuccio, Luca, Inanç, Nevsun, Özkızıltaş, Burcugül, Bartoloni, Elena, Sebastian, Agata, Romão, Vasco C., Solans, Roser, Pasoto, Sandra G., Rischmueller, Maureen, Galisteo, Carlos, Suzuki, Yasunori, Trevisani, Virginia Fernandes Moça, Fugmann, Cecilia, González-García, Andrés, Carubbi, Francesco, Jurcut, Ciprian, Shimizu, Toshimasa, Retamozo, Soledad, Atzeni, Fabiola, Hofauer, Benedikt, Melchor-Díaz, Sheila, Gheita, Tamer, López-Dupla, Miguel, Fonseca-Aizpuru, Eva, Giacomelli, Roberto, Vázquez, Marcos, Consani, Sandra, Akasbi, Miriam, Nakamura, Hideki, Szántó, Antónia, Farris, A. Darise, Wang, Li, Mandl, Thomas, Gattamelata, Angelica, Kilic, Levent, Pirkmajer, Katja Perdan, Abacar, Kerem, Tufan, Abdurrahman, de Vita, Salvatore, Bootsma, Hendrika, and Ramos-Casals, Manuel

Published
2023
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5. The management of patients with inflammatory bowel disease-associated spondyloarthritis: Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and Italian Society of Rheumatology (SIR) recommendations based on a pseudo-Delphi consensus

Author

Macaluso, F, Caprioli, F, Benedan, L, Bezzio, C, Caporali, R, Cauli, A, Chimenti, M, Ciccia, F, D'Angelo, S, Fantini, M, Festa, S, Iannone, F, Lubrano, E, Mariani, P, Papi, C, Provenzano, G, Pugliese, D, Rispo, A, Saibeni, S, Salvarani, C, Variola, A, Zenga, M, Armuzzi, A, Orlando, A, Gerli, R, Macaluso, Fabio Salvatore, Caprioli, Flavio, Benedan, Laura, Bezzio, Cristina, Caporali, Roberto, Cauli, Alberto, Chimenti, Maria Sole, Ciccia, Francesco, D'Angelo, Salvatore, Fantini, Massimo Claudio, Festa, Stefano, Iannone, Florenzo, Lubrano, Ennio, Mariani, Paolo, Papi, Claudio, Provenzano, Giuseppe, Pugliese, Daniela, Rispo, Antonio, Saibeni, Simone, Salvarani, Carlo, Variola, Angela, Zenga, Mariangela, Armuzzi, Alessandro, Orlando, Ambrogio, Gerli, Roberto, Macaluso, F, Caprioli, F, Benedan, L, Bezzio, C, Caporali, R, Cauli, A, Chimenti, M, Ciccia, F, D'Angelo, S, Fantini, M, Festa, S, Iannone, F, Lubrano, E, Mariani, P, Papi, C, Provenzano, G, Pugliese, D, Rispo, A, Saibeni, S, Salvarani, C, Variola, A, Zenga, M, Armuzzi, A, Orlando, A, Gerli, R, Macaluso, Fabio Salvatore, Caprioli, Flavio, Benedan, Laura, Bezzio, Cristina, Caporali, Roberto, Cauli, Alberto, Chimenti, Maria Sole, Ciccia, Francesco, D'Angelo, Salvatore, Fantini, Massimo Claudio, Festa, Stefano, Iannone, Florenzo, Lubrano, Ennio, Mariani, Paolo, Papi, Claudio, Provenzano, Giuseppe, Pugliese, Daniela, Rispo, Antonio, Saibeni, Simone, Salvarani, Carlo, Variola, Angela, Zenga, Mariangela, Armuzzi, Alessandro, Orlando, Ambrogio, and Gerli, Roberto

Abstract

Spondyloarthritis (SpA) is the most frequent extraintestinal manifestation in patients with inflammatory bowel diseases (IBD). When IBD and spondyloarthritis coexist, musculoskeletal and intestinal disease features should be considered when planning a therapeutic strategy. Treatment options for IBD and SpA have expanded enormously over the last few years, but randomized controlled trials with specific endpoints focused on SpA are not available in the IBD setting. To address this important clinical topic, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and the Italian Society of Rheumatology (SIR) jointly planned to draw updated therapeutic recommendations for IBD-associated SpA using a pseudo-Delphi method. This document presents the official recommendations of IG-IBD and SIR on the management of IBD-associated SpA in the form of 34 statements and 4 therapeutic algorithms. It is intended to be a reference guide for gastroenterologists and rheumatologists dealing with IBD-associated SpA.

Published
2024

6. Treatment with COLchicine in hospitalized patients affected by COVID-19: The COLVID-19 trial

Author

Perricone, C, Scarsi, M, Brucato, A, Pisano, P, Pigatto, E, Becattini, C, Cingolani, A, Tiso, F, Prota, R, Tomasoni, L, Cutolo, M, Tardella, M, Rozza, D, Zerbino, C, Andreoni, M, Poletti, V, Bartoloni, E, Gerli, R, Cafaro, G, Mendeni, M, Colombo, E, Medico, M, Cabras, P, Schiesaro, M, Franco, L, Fantoni, M, Friso, L, Gallo, V, Franceschini, F, Paolino, S, Salaffi, F, Scire, C, Zanetti, A, Diana, C, Passaro, A, Foti, R, Serino, F, Cassol, M, Bucaneve, G, Rocchi, R, Perricone C., Scarsi M., Brucato A., Pisano P., Pigatto E., Becattini C., Cingolani A., Tiso F., Prota R., Tomasoni L. R., Cutolo M., Tardella M., Rozza D., Zerbino C., Andreoni M., Poletti V., Bartoloni E., Gerli R., Cafaro G., Mendeni M., Colombo E., Medico M. D., Cabras P., Schiesaro M. G., Franco L., Fantoni M., Friso L., Gallo V., Franceschini F., Paolino S., Salaffi F., Scire C. A., Zanetti A., Diana C., Passaro A., Foti R., Serino F. S., Cassol M., Bucaneve G., Rocchi R. E., Perricone, C, Scarsi, M, Brucato, A, Pisano, P, Pigatto, E, Becattini, C, Cingolani, A, Tiso, F, Prota, R, Tomasoni, L, Cutolo, M, Tardella, M, Rozza, D, Zerbino, C, Andreoni, M, Poletti, V, Bartoloni, E, Gerli, R, Cafaro, G, Mendeni, M, Colombo, E, Medico, M, Cabras, P, Schiesaro, M, Franco, L, Fantoni, M, Friso, L, Gallo, V, Franceschini, F, Paolino, S, Salaffi, F, Scire, C, Zanetti, A, Diana, C, Passaro, A, Foti, R, Serino, F, Cassol, M, Bucaneve, G, Rocchi, R, Perricone C., Scarsi M., Brucato A., Pisano P., Pigatto E., Becattini C., Cingolani A., Tiso F., Prota R., Tomasoni L. R., Cutolo M., Tardella M., Rozza D., Zerbino C., Andreoni M., Poletti V., Bartoloni E., Gerli R., Cafaro G., Mendeni M., Colombo E., Medico M. D., Cabras P., Schiesaro M. G., Franco L., Fantoni M., Friso L., Gallo V., Franceschini F., Paolino S., Salaffi F., Scire C. A., Zanetti A., Diana C., Passaro A., Foti R., Serino F. S., Cassol M., Bucaneve G., and Rocchi R. E.

Abstract

Objective: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. Design: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. Results: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F<275 mmHg (P=0.005), AST>40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group. Conclusion: Colchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome.

Published
2023

7. A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts

Author

Farias, Fabiana H. G., Dahlqvist, Johanna, Kozyrev, Sergey V., Leonard, Dag, Wilbe, Maria, Abramov, Sergei N., Alexsson, Andrei, Pielberg, Gerli R., Hansson-Hamlin, Helene, Andersson, Göran, Tandre, Karolina, Bengtsson, Anders A., Sjöwall, Christopher, Svenungsson, Elisabet, Gunnarsson, Iva, Rantapää-Dahlqvist, Solbritt, Syvänen, Ann-Christine, Sandling, Johanna K., Eloranta, Maija-Leena, Rönnblom, Lars, and Lindblad-Toh, Kerstin

Published
2019
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9. Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study

Author

Brito-Zerón, Pilar, primary, Flores-Chávez, Alejandra, additional, Horváth, Ildiko Fanny, additional, Rasmussen, Astrid, additional, Li, Xiaomei, additional, Olsson, Peter, additional, Vissink, Arjan, additional, Priori, Roberta, additional, Armagan, Berkan, additional, Hernandez-Molina, Gabriela, additional, Praprotnik, Sonja, additional, Quartuccio, Luca, additional, Inanç, Nevsun, additional, Özkızıltaş, Burcugül, additional, Bartoloni, Elena, additional, Sebastian, Agata, additional, Romão, Vasco C., additional, Solans, Roser, additional, Pasoto, Sandra G., additional, Rischmueller, Maureen, additional, Galisteo, Carlos, additional, Suzuki, Yasunori, additional, Trevisani, Virginia Fernandes Moça, additional, Fugmann, Cecilia, additional, González-García, Andrés, additional, Carubbi, Francesco, additional, Jurcut, Ciprian, additional, Shimizu, Toshimasa, additional, Retamozo, Soledad, additional, Atzeni, Fabiola, additional, Hofauer, Benedikt, additional, Melchor-Díaz, Sheila, additional, Gheita, Tamer, additional, López-Dupla, Miguel, additional, Fonseca-Aizpuru, Eva, additional, Giacomelli, Roberto, additional, Vázquez, Marcos, additional, Consani, Sandra, additional, Akasbi, Miriam, additional, Nakamura, Hideki, additional, Szántó, Antónia, additional, Farris, A. Darise, additional, Wang, Li, additional, Mandl, Thomas, additional, Gattamelata, Angelica, additional, Kilic, Levent, additional, Pirkmajer, Katja Perdan, additional, Abacar, Kerem, additional, Tufan, Abdurrahman, additional, de Vita, Salvatore, additional, Bootsma, Hendrika, additional, Ramos-Casals, Manuel, additional, Arends, S., additional, Treppo, E., additional, Longhino, S., additional, Manfrè, V., additional, Rizzo, M., additional, Baldini, C., additional, Bombardieri, S., additional, Bandeira, M., additional, Silvéiro-António, M., additional, Seror, R., additional, Mariette, X., additional, Nordmark, G., additional, Danda, D., additional, Wiland, P., additional, Gerli, R., additional, Kwok, S.K., additional, Park, S.H., additional, Kvarnstrom, M., additional, Wahren-Herlenius, M., additional, Downie-Doyle, S., additional, Sene, D., additional, Isenberg, D., additional, Valim, V., additional, Devauchelle-Pensec, V., additional, Saraux, A., additional, Morel, J., additional, Morcillo, C., additional, Díaz Cuiza, P.E., additional, Herrera, B.E., additional, González-de-Paz, L., additional, and Sisó-Almirall, A., additional

Published
2023
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10. Increased COVID-19 mortality in patients with rheumatic diseases: results from the CONTROL-19 study by the Italian Society for Rheumatology

Author

Zanetti, A, Carrara, G, Landolfi, G, Rozza, D, Chighizola, C, Alunno, A, Andreoli, L, Caporali, R, Gerli, R, Sebastiani, G, Valesini, G, Sinigaglia, L, Raffeiner, B, Lomater, C, Caprioli, M, Fredi, M, Romeo, N, Cuomo, G, Vadacca, M, Scire, C, Zanetti A., Carrara G., Landolfi G., Rozza D., Chighizola C. B., Alunno A., Andreoli L., Caporali R., Gerli R., Sebastiani G. D., Valesini G., Sinigaglia L., Raffeiner B., Lomater C., Caprioli M., Fredi M., Romeo N., Cuomo G., Vadacca M., Scire C. A., Zanetti, A, Carrara, G, Landolfi, G, Rozza, D, Chighizola, C, Alunno, A, Andreoli, L, Caporali, R, Gerli, R, Sebastiani, G, Valesini, G, Sinigaglia, L, Raffeiner, B, Lomater, C, Caprioli, M, Fredi, M, Romeo, N, Cuomo, G, Vadacca, M, Scire, C, Zanetti A., Carrara G., Landolfi G., Rozza D., Chighizola C. B., Alunno A., Andreoli L., Caporali R., Gerli R., Sebastiani G. D., Valesini G., Sinigaglia L., Raffeiner B., Lomater C., Caprioli M., Fredi M., Romeo N., Cuomo G., Vadacca M., and Scire C. A.

Abstract

Objective To investigate differences in coronavirus disease 2019 (COVID-19) mortality between patients with rheumatic musculoskeletal diseases (RMD) and the general population in Italy. Methods We analysed the data from the national surveillance study promoted by the Italian Society for Rheumatology (CONTROL-19 database) including patients with RMD and COVID-19 between 26 March 2020 and 29 November 2020, compared with official data from the Italian population (within the same period) adjusted for age, sex and geographic location. The main outcome of the analyses was mortality. The relationship between RMD and mortality was analysed using adjusted logistic models and sensitivity analyses were conducted to support the robustness of our results. Results We included 668 RMD patients (62.7% with inflammatory arthritis, 28.6% with systemic autoimmune diseases), who had a mean age of 58.4 years and of which 66% were female. Compared to the general population, the RMD population showed an increased risk of death (OR 3.10 (95% CI 2.29–4.12)), independently from the differences in age and sex distribution. Even after considering the potential influence of surveillance bias, the OR was 2.08 (95% CI: 1.55–2.73). Such excess of risk was more evident in the subgroup of younger patients, and more consistent in women. Subjects with systemic autoimmune diseases showed a higher risk of death than patients with any other RMDs. Conclusions Patients with RMD and COVID-19 infection evidenced a significant increase in mortality during the first pandemic phases in Italy. These findings support the need for strong SARS-CoV-2 prevention in patients with rheumatic diseases.

Published
2022

11. Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies

Author

Cavagna, L, Meloni, F, Meyer, A, Sambataro, G, Belliato, M, De Langhe, E, Cavazzana, I, Pipitone, N, Triantafyllias, K, Mosca, M, Barsotti, S, Zampogna, G, Biglia, A, Emmi, G, De Visser, M, Van Der Kooi, A, Parronchi, P, Hirschi, S, da Silva, J, Scire, C, Furini, F, Giannini, M, Martinez Gonzalez, O, Damian, L, Piette, Y, Smith, V, Mera-Valera, A, Bachiller-Corral, J, Cabezas Rodriguez, I, Brandy-Garcia, A, Maurier, F, Perrin, J, Gonzalez-Moreno, J, Drott, U, Delbruck, C, Schwarting, A, Arrigoni, E, Sebastiani, G, Iuliano, A, Nannini, C, Quartuccio, L, Rodriguez Cambron, A, Blazquez Canamero, M, Villa Blanco, I, Cagnotto, G, Pesci, A, Luppi, F, Dei, G, Romero Bueno, F, Franceschini, F, Chiapparoli, I, Zanframundo, G, Lettieri, S, De Stefano, L, Cutolo, M, Mathieu, A, Piga, M, Prieto-Gonzalez, S, Moraes-Fontes, M, Fonseca, J, Jovani, V, Riccieri, V, Santaniello, A, Montfort, S, Bilocca, D, Erre, G, Bartoloni, E, Gerli, R, Monti, M, Lorenz, H, Sambataro, D, Bellando Randone, S, Schneider, U, Valenzuela, C, Lopez-Mejias, R, Cifrian, J, Mejia, M, Gonzalez Perez, M, Wendel, S, Fornaro, M, De Luca, G, Orsolini, G, Rossini, M, Dieude, P, Knitza, J, Castaneda, S, Voll, R, Rojas-Serrano, J, Valentini, A, Vancheri, C, Matucci-Cerinic, M, Feist, E, Codullo, V, Iannone, F, Distler, J, Montecucco, C, Gonzalez-Gay, M, Cavagna L., Meloni F., Meyer A., Sambataro G., Belliato M., De Langhe E., Cavazzana I., Pipitone N., Triantafyllias K., Mosca M., Barsotti S., Zampogna G., Biglia A., Emmi G., De Visser M., Van Der Kooi A., Parronchi P., Hirschi S., da Silva J. A. P., Scire C. A., Furini F., Giannini M., Martinez Gonzalez O., Damian L., Piette Y., Smith V., Mera-Valera A., Bachiller-Corral J., Cabezas Rodriguez I., Brandy-Garcia A. M., Maurier F., Perrin J., Gonzalez-Moreno J., Drott U., Delbruck C., Schwarting A., Arrigoni E., Sebastiani G. D., Iuliano A., Nannini C., Quartuccio L., Rodriguez Cambron A. B., Blazquez Canamero M. A., Villa Blanco I., Cagnotto G., Pesci A., Luppi F., Dei G., Romero Bueno F. I., Franceschini F., Chiapparoli I., Zanframundo G., Lettieri S., De Stefano L., Cutolo M., Mathieu A., Piga M., Prieto-Gonzalez S., Moraes-Fontes M. F., Fonseca J. E., Jovani V., Riccieri V., Santaniello A., Montfort S., Bilocca D., Erre G. L., Bartoloni E., Gerli R., Monti M. C., Lorenz H. M., Sambataro D., Bellando Randone S., Schneider U., Valenzuela C., Lopez-Mejias R., Cifrian J., Mejia M., Gonzalez Perez M. -I., Wendel S., Fornaro M., De Luca G., Orsolini G., Rossini M., Dieude P., Knitza J., Castaneda S., Voll R. E., Rojas-Serrano J., Valentini A., Vancheri C., Matucci-Cerinic M., Feist E., Codullo V., Iannone F., Distler J. H., Montecucco C., Gonzalez-Gay M. A., Cavagna, L, Meloni, F, Meyer, A, Sambataro, G, Belliato, M, De Langhe, E, Cavazzana, I, Pipitone, N, Triantafyllias, K, Mosca, M, Barsotti, S, Zampogna, G, Biglia, A, Emmi, G, De Visser, M, Van Der Kooi, A, Parronchi, P, Hirschi, S, da Silva, J, Scire, C, Furini, F, Giannini, M, Martinez Gonzalez, O, Damian, L, Piette, Y, Smith, V, Mera-Valera, A, Bachiller-Corral, J, Cabezas Rodriguez, I, Brandy-Garcia, A, Maurier, F, Perrin, J, Gonzalez-Moreno, J, Drott, U, Delbruck, C, Schwarting, A, Arrigoni, E, Sebastiani, G, Iuliano, A, Nannini, C, Quartuccio, L, Rodriguez Cambron, A, Blazquez Canamero, M, Villa Blanco, I, Cagnotto, G, Pesci, A, Luppi, F, Dei, G, Romero Bueno, F, Franceschini, F, Chiapparoli, I, Zanframundo, G, Lettieri, S, De Stefano, L, Cutolo, M, Mathieu, A, Piga, M, Prieto-Gonzalez, S, Moraes-Fontes, M, Fonseca, J, Jovani, V, Riccieri, V, Santaniello, A, Montfort, S, Bilocca, D, Erre, G, Bartoloni, E, Gerli, R, Monti, M, Lorenz, H, Sambataro, D, Bellando Randone, S, Schneider, U, Valenzuela, C, Lopez-Mejias, R, Cifrian, J, Mejia, M, Gonzalez Perez, M, Wendel, S, Fornaro, M, De Luca, G, Orsolini, G, Rossini, M, Dieude, P, Knitza, J, Castaneda, S, Voll, R, Rojas-Serrano, J, Valentini, A, Vancheri, C, Matucci-Cerinic, M, Feist, E, Codullo, V, Iannone, F, Distler, J, Montecucco, C, Gonzalez-Gay, M, Cavagna L., Meloni F., Meyer A., Sambataro G., Belliato M., De Langhe E., Cavazzana I., Pipitone N., Triantafyllias K., Mosca M., Barsotti S., Zampogna G., Biglia A., Emmi G., De Visser M., Van Der Kooi A., Parronchi P., Hirschi S., da Silva J. A. P., Scire C. A., Furini F., Giannini M., Martinez Gonzalez O., Damian L., Piette Y., Smith V., Mera-Valera A., Bachiller-Corral J., Cabezas Rodriguez I., Brandy-Garcia A. M., Maurier F., Perrin J., Gonzalez-Moreno J., Drott U., Delbruck C., Schwarting A., Arrigoni E., Sebastiani G. D., Iuliano A., Nannini C., Quartuccio L., Rodriguez Cambron A. B., Blazquez Canamero M. A., Villa Blanco I., Cagnotto G., Pesci A., Luppi F., Dei G., Romero Bueno F. I., Franceschini F., Chiapparoli I., Zanframundo G., Lettieri S., De Stefano L., Cutolo M., Mathieu A., Piga M., Prieto-Gonzalez S., Moraes-Fontes M. F., Fonseca J. E., Jovani V., Riccieri V., Santaniello A., Montfort S., Bilocca D., Erre G. L., Bartoloni E., Gerli R., Monti M. C., Lorenz H. M., Sambataro D., Bellando Randone S., Schneider U., Valenzuela C., Lopez-Mejias R., Cifrian J., Mejia M., Gonzalez Perez M. -I., Wendel S., Fornaro M., De Luca G., Orsolini G., Rossini M., Dieude P., Knitza J., Castaneda S., Voll R. E., Rojas-Serrano J., Valentini A., Vancheri C., Matucci-Cerinic M., Feist E., Codullo V., Iannone F., Distler J. H., Montecucco C., and Gonzalez-Gay M. A.

Abstract

Objective To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods We conducted a multicentre, international, retrospective cohort study. Results 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusion The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Published
2022

12. POS1463 FACTORS ASSOCIATED WITH DISEASE DAMAGE AT 20 YEAR FOLLOW-UP IN AN ITALIAN MULTICENTER SJÖGREN’S SYNDROME COHORT

Author

Cafaro, G., primary, Ferro, F., additional, Dal Pozzolo, R., additional, Fulvio, G., additional, Bruno, L., additional, Fonzetti, S., additional, La Rocca, G., additional, Dei, B., additional, Falaschi, S., additional, Perricone, C., additional, Gerli, R., additional, Baldini, C., additional, and Bartoloni, E., additional

Published
2023
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14. Polymyalgia Rheumatica

Author

Bartoloni, E., primary, Pucci, G., additional, Alunno, A., additional, Gerli, R., additional, and Schillaci, G., additional

Published
2017
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15. The Italian society of rheumatology clinical practice guidelines for the management of polymyalgia rheumatic

Author

Ughi, N, Sebastiani, G, Gerli, R, Salvaran, C, Parisi, S, Ariani, A, Prevete, I, Manara, M, Rumi, F, Scire, C, Bortoluzzi, A, Ughi N., Sebastiani G. D., Gerli R., Salvaran C., Parisi S., Ariani A., Prevete I., Manara M., Rumi F., Scire C. A., Bortoluzzi A., Ughi, N, Sebastiani, G, Gerli, R, Salvaran, C, Parisi, S, Ariani, A, Prevete, I, Manara, M, Rumi, F, Scire, C, Bortoluzzi, A, Ughi N., Sebastiani G. D., Gerli R., Salvaran C., Parisi S., Ariani A., Prevete I., Manara M., Rumi F., Scire C. A., and Bortoluzzi A.

Abstract

Objective: To provide evidence-based up-to-date recommendations for the management of patients with a definite diagnosis of polymyalgia rheumatica (PMR). Methods: A systematic literature review was performed to find the existing clinical practice guidelines (CPGs) on PMR and the framework of the Guidelines International Network Adaptation Working Group was used to appraise (AGREE II), synthesize, and customize the recommendations according to the needs of the Italian healthcare context. Rheumatologists on behalf of the Italian Society of Rheumatology (SIR) and from the SIR Epidemiology Unit joined the working group and identified the key health questions on PMR to guide the systematic literature review. Physicians, including general practitioners and specialists, and health professionals who manage PMR in the clinical practice were the target audience. The final recommendations were rated externally by a multi-disciplinary and multi-professional group of stakeholders. Results: From the systematic search in databases (Medline, Embase) and grey literature, 3 CPGs were identified and appraised by two independent raters. Combining the statements and the evidence from these CPGs, 9 recommendations were developed by endorsement or adaptation in response to the initial key health questions. The quality of evidence was graded and the working group discussed the final recommendations in view of their implementation in the Italian healthcare context. Conclusions: In absence of national guidelines so far, these recommendations are the first to provide guidance for the management of patients with a diagnosis of PMR in Italy and they are expected to ensure the best evidence-based clinical practice for this disease.

Published
2020

16. Reply to the letter to the editor: The italian society of rheumatology clinical practice guidelines for the management of polymyalgia rheumatica

Author

Ughi, N, Sebastiani, G, Gerli, R, Salvarani, C, Parisi, S, Ariani, A, Prevete, I, Manara, M, Rumi, F, Scire, C, Bortoluzzi, A, Ughi N., Sebastiani G. D., Gerli R., Salvarani C., Parisi S., Ariani A., Prevete I., Manara M., Rumi F., Scire C. A., Bortoluzzi A., Ughi, N, Sebastiani, G, Gerli, R, Salvarani, C, Parisi, S, Ariani, A, Prevete, I, Manara, M, Rumi, F, Scire, C, Bortoluzzi, A, Ughi N., Sebastiani G. D., Gerli R., Salvarani C., Parisi S., Ariani A., Prevete I., Manara M., Rumi F., Scire C. A., and Bortoluzzi A.

Published
2020

19. AB0441 PREDICTORS OF CLASI RESPONSE OVER TIME IN A MULTICENTRIC REAL LIFE COHORT OF SLE PATIENTS TREATED WITH BELIMUMAB

Author

Gatto, M., primary, Depascale, R., additional, Tincani, A., additional, Emmi, G., additional, Scarpato, S., additional, Conti, F., additional, Govoni, M., additional, Mosca, M., additional, Gerosa, M., additional, Bozzolo, E., additional, Canti, V., additional, Gabrielli, A., additional, Gremese, E., additional, De Vita, S., additional, Ciccia, F., additional, Salvarani, C., additional, Rossini, M., additional, Faggioli, P., additional, Laria, A., additional, De Paulis, A., additional, Gerli, R., additional, Brunetta, E., additional, Mathieu, A., additional, Selmi, C., additional, De Angelis, R., additional, Negrini, S., additional, Zen, M., additional, Doria, A., additional, and Iaccarino, L., additional

Published
2022
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20. List of Contributors

Author

Alunno, A., primary, Appel, S., additional, Astorri, E., additional, Baldini, C., additional, Barone, F., additional, Bartoloni, E., additional, Bombardieri, M., additional, Bombardieri, S., additional, Bowman, S.J., additional, Campos, J., additional, Carubbi, F., additional, Cipriani, P., additional, Colafrancesco, S., additional, De Vita, S., additional, Del Papa, N., additional, Devauchelle-Pensec, V., additional, Felten, R., additional, Fisher, B.A., additional, Fox, C.M., additional, Fox, R.I., additional, Gandolfo, S., additional, Gerli, R., additional, Giacomelli, R., additional, Gottenberg, J.-E., additional, Jonsson, R., additional, Kapsogeorgou, E.K., additional, Kyttaris, V.C., additional, Lucchesi, D., additional, Lunardi, C., additional, Manoussakis, M.N., additional, Mavragani, C.P., additional, Patuzzo, G., additional, Perricone, C., additional, Pers, J.-O., additional, Pitzalis, C., additional, Priori, R., additional, Quartuccio, L., additional, Shoenfeld, Y., additional, Sibilia, J., additional, Tinazzi, E., additional, Tsokos, G.C., additional, Tzioufas, A.G., additional, Valesini, G., additional, Vitali, C., additional, and Youinou, P., additional

Published
2016
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25. Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

Author

Pezoulas, V.C. Goules, A. Kalatzis, F. Chatzis, L. Kourou, K.D. Venetsanopoulou, A. Exarchos, T.P. Gandolfo, S. Votis, K. Zampeli, E. Burmeister, J. May, T. Marcelino Pérez, M. Lishchuk, I. Chondrogiannis, T. Andronikou, V. Varvarigou, T. Filipovic, N. Tsiknakis, M. Baldini, C. Bombardieri, M. Bootsma, H. Bowman, S.J. Shahnawaz Soyfoo, M. Parisis, D. Delporte, C. Devauchelle-Pensec, V. Pers, J.-O. Dörner, T. Bartoloni, E. Gerli, R. Giacomelli, R. Jonsson, R. Ng, W.-F. Priori, R. Ramos-Casals, M. Sivils, K. Skopouli, F. Torsten, W. A. G. van Roon, J. Xavier, M. De Vita, S. Tzioufas, A.G. Fotiadis, D.I.

Abstract

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s)

Published
2022

26. GENDER AND FIBROMYALGIA SEVERITY: REAL LIFE DATA FROM THE ITALIAN REGISTRY

Author

Batticciotto, A, Campanaro, F, Atzeni, F, Alciati, A, Di Carlo, M, Bazzichi, L, Govoni, M, Biasi, G, Di Franco, M, Mozzani, F, Gremese, E, Dagna, L, Fischetti, F, Giacomelli, R, Guiducci, S, Guggino, G, Bentivegna, M, Gerli, R, Salvarani, C, Bajocchi, G, Ghini, M, Iannone, F, Giorgi, V, Farah, S, Bonazza, S, Barbagli, S, Gioia, C, Capacci, A, Cavalli, G, Carubbi, F, Nacci, F, Ilenia, R, Sinigaglia, L, Cutolo, M, Cappelli, A, Sarzi-Puttini, P, Salaffi, F, Batticciotto, A, Campanaro, F, Atzeni, F, Alciati, A, Di Carlo, M, Bazzichi, L, Govoni, M, Biasi, G, Di Franco, M, Mozzani, F, Gremese, E, Dagna, L, Fischetti, F, Giacomelli, R, Guiducci, S, Guggino, G, Bentivegna, M, Gerli, R, Salvarani, C, Bajocchi, G, Ghini, M, Iannone, F, Giorgi, V, Farah, S, Bonazza, S, Barbagli, S, Gioia, C, Capacci, A, Cavalli, G, Carubbi, F, Nacci, F, Ilenia, R, Sinigaglia, L, Cutolo, M, Cappelli, A, Sarzi-Puttini, P, and Salaffi, F

Subjects
Fibromyalgia, Rheumatology
Abstract

Background: Fibromyalgia (FM) patients report chronic widespread pain, fatigue, cognitive difficulties and sleep disturbances, often associated with anxiety and/or depression (1). FM syndrome more frequently affects women and many papers describe gender-related differences in the perception, description and expression of pain (2), but up to now, the impact of gender on the clinical severity of FM is still a controversial topic. Objectives: The aim of this study was to analyse the data from a web-based registry of FM patients in order to detect a relationship between gender and disease severity. Methods: Adult patients with FM, diagnosed on the basis of the 2010/2011 American College of Rheumatology (ACR) diagnostic criteria (3), were recruited at 19 Italian rheumatology centres between November 2018 and April 2019. Those affected by other conditions that could interfere with the assessment of FM, e.g. psychiatric disorders, were excluded from the study. The severity of the disease was evaluated by validated FM-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR) (4), the modified Fibromyalgia Assessment Status (ModFAS) questionnaire (5), and the Polysymptomatic Distress Scale (PDS) (6). The data obtained were collected in the Italian Fibromyalgia Registry, an online registry created with the support of the Italian Society of Rheumatology (SIR). Results: We analyse data from 2.381 patients affected by FM, 2.184 females (91.7%) and 197 males. No significant differences in mean age, disease duration, or BMI between the two genders were reported. The women expressed greater disease burden as indicated by higher scores for each completed test: higher mean ModFAS score (25.23 ± 8.83 Vs 23.37 ± 9.22; p = 0.005), mean FIQR score (58.62 ± 23.22 Vs 51.68 ± 23.06; p

Published
2021

27. Influence of the age at diagnosis in the disease expression of primary Sjögren's syndrome: Analysis of 12,753 patients from the Sjögren Big Data Consortium

Author

Retamozo, S., Acar-Denizli, N., Horváth, I. F., Ng, W. -F, Rasmussen, A., Dong, X., Li, X., Baldini, C., Olsson, P., Priori, R., Seror, R., Gottenberg, J. -E, Kruize, A. A., Hernandez-Molina, G., Vissink, A., Sandhya, P., Armagan, B., Quartuccio, L., Sebastian, A., Praprotnik, S., Bartoloni, E., Kwok, S. -K, Kvarnstrom, M., Rischmueller, M., Soláns-Laqué, R., Sene, D., Pasoto, S. G., Suzuki, Y., Isenberg, D. A., Valim, V., Nordmark, G., Nakamura, H., Virginia Trevisani, Hofauer, B., Sisó-Almirall, A., Giacomelli, R., Devauchelle-Pensec, V., Bombardieri, M., Atzeni, F., Hammenfors, D., Maure, B., Carsons, S. E., Gheita, T., Sánchez-Berná, I., López-Dupla, M., Morel, J., Inanç, N., Fonseca-Aizpuru, E., Morcillo, C., Vollenweider, C., Melchor, S., Vázquez, M., Díaz-Cuiza, E., Consani-Fernández, S., De-Miguel-Campo, B., Szántó, A., Bombardieri, S., Gattamelata, A., Hinrichs, A., Sánchez-Guerrero, J., Danda, D., Kilic, L., Vita, S., Wiland, P., Gerli, R., Park, S. -H, Wahren-Herlenius, M., Bootsma, H., Mariette, X., Ramos-Casals, M., Brito-Zerón, P., Translational Immunology Groningen (TRIGR), and Personalized Healthcare Technology (PHT)

Subjects
immunological markers, MANIFESTATIONS, age, Sjogren's syndrome, ONSET, YOUNG, MANAGEMENT, LYMPHOMA, disease phenotype, CLASSIFICATION CRITERIA, CONSENSUS, PROJECT, SALIVARY FLOW
Abstract

Objective. To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjogren's syndrome (pSS). Methods. By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. Results. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of 95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R-2 0.87) and the frequency of abnormal oral tests (adjusted R-2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). Conclusion. The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Published
2021

29. Erratum: Management of adult-onset Still's disease with interleukin-1 inhibitors: Evidence- And consensus-based statements by a panel of Italian experts (Arthritis Res Ther (2019) 21:275 DOI: 10.1186/s13075-019-2021-9)

Author

Colafrancesco, S., Manara, M., Bortoluzzi, A., Serban, T., Bianchi, G., Cantarini, L., Ciccia, F., Dagna, L., Govoni, M., Montecucco, C., Priori, R., Ravelli, A., Sfriso, P., Sinigaglia, L., Alivernini, S., Baldissera, E., Bartoloni, E., Berti, A., Bugatti, S., Camellino, D., Cammelli, D., Caporali, R., Caso, F., Cavallaro, E., Cavalli, G., Colaci, M., Costa, L., Di Scala, G., Emmi, G., Frassi, M., Gerli, R., Giacomelli, R., Gremese, E., Iannone, F., Lapadula, G., Leveghi, L., Lopalco, G., Manna, R., Marotto, D., Mathieu, A., Neri, R., Patisso, I., Piga, M., Punzi, L., Romano, M., Ruscitti, P., Salvarani, C., Scarpa, R., Scrivo, R., Talarico, R., Verrecchia, E., Viapiana, O., Vitale, A., Vitiello, G., Colafrancesco, S., Manara, M., Bortoluzzi, A., Serban, T., Bianchi, G., Cantarini, L., Ciccia, F., Dagna, L., Govoni, M., Montecucco, C., Priori, R., Ravelli, A., Sfriso, P., Sinigaglia, L., Alivernini, S., Baldissera, E., Bartoloni, E., Berti, A., Bugatti, S., Camellino, D., Cammelli, D., Caporali, R., Caso, F., Cavallaro, E., Cavalli, G., Colaci, M., Costa, L., Di Scala, G., Emmi, G., Frassi, M., Gerli, R., Giacomelli, R., Gremese, E., Iannone, F., Lapadula, G., Leveghi, L., Lopalco, G., Manna, R., Marotto, D., Mathieu, A., Neri, R., Patisso, I., Piga, M., Punzi, L., Romano, M., Ruscitti, P., Salvarani, C., Scarpa, R., Scrivo, R., Talarico, R., Verrecchia, E., Viapiana, O., Vitale, A., and Vitiello, G.

Abstract

Following publication of the original article [1], it was brought to our attention that the AOSD Consensus Group was incorrectly tagged and therefore not searchable. The publishers apologize for this error.

Published
2020

33. The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts’ Consensus

Author

Giacomelli, R. Afeltra, A. Bartoloni, E. Berardicurti, O. Bombardieri, M. Bortoluzzi, A. Carubbi, F. Caso, F. Cervera, R. Ciccia, F. Cipriani, P. Coloma-Bazán, E. Conti, F. Costa, L. D'Angelo, S. Distler, O. Feist, E. Foulquier, N. Gabini, M. Gerber, V. Gerli, R. Grembiale, R.D. Guggino, G. Hoxha, A. Iagnocco, A. Jordan, S. Kahaleh, B. Lauper, K. Liakouli, V. Lubrano, E. Margiotta, D. Naty, S. Navarini, L. Perosa, F. Perricone, C. Perricone, R. Prete, M. Pers, J.-O. Pitzalis, C. Priori, R. Rivellese, F. Ruffatti, A. Ruscitti, P. Scarpa, R. Shoenfeld, Y. Triolo, G. Tzioufas, A.

Abstract

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients. © 2020

Published
2021

34. Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort

Author

Gatto, Dario Mattia, Saccon, F., Andreoli, L., Bartoloni, E., Benvenuti, F., Bortoluzzi, A., Bozzolo, E., Brunetta, E., Canti, V., Cardinaletti, P., Ceccarelli, F., Ciccia, F., Conti, Francesco, De Marchi, G., de Paulis, A., De Vita, S., Emmi, G., Faggioli, P., Fasano, S., Fredi, M., Gabrielli, Francesca Augusta, Gasparotto, M., Gerli, R., Gerosa, M., Govoni, M., Gremese, Elisa, Laria, A., Larosa, M., Mosca, Miranda, Orsolini, G., Pazzola, G., Petricca, Luca, Ramirez, G. A., Regola, F., Rossi, F. W., Rossini, Paolo Maria, Salvarani, C., Scarpato, S., Tani, C., Tincani, A., Ubiali, T., Urban, M. L., Zen, Maria Pia, Doria, A., Iaccarino, Ludovica, Gatto M., Conti F., Gabrielli A., Gremese E. (ORCID:0000-0002-2248-1058), Mosca M., Petricca L., Rossini M. (ORCID:0000-0003-2665-534X), Zen M., Iaccarino L., Gatto, Dario Mattia, Saccon, F., Andreoli, L., Bartoloni, E., Benvenuti, F., Bortoluzzi, A., Bozzolo, E., Brunetta, E., Canti, V., Cardinaletti, P., Ceccarelli, F., Ciccia, F., Conti, Francesco, De Marchi, G., de Paulis, A., De Vita, S., Emmi, G., Faggioli, P., Fasano, S., Fredi, M., Gabrielli, Francesca Augusta, Gasparotto, M., Gerli, R., Gerosa, M., Govoni, M., Gremese, Elisa, Laria, A., Larosa, M., Mosca, Miranda, Orsolini, G., Pazzola, G., Petricca, Luca, Ramirez, G. A., Regola, F., Rossi, F. W., Rossini, Paolo Maria, Salvarani, C., Scarpato, S., Tani, C., Tincani, A., Ubiali, T., Urban, M. L., Zen, Maria Pia, Doria, A., Iaccarino, Ludovica, Gatto M., Conti F., Gabrielli A., Gremese E. (ORCID:0000-0002-2248-1058), Mosca M., Petricca L., Rossini M. (ORCID:0000-0003-2665-534X), Zen M., and Iaccarino L.

Abstract

Background: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). Aim: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. Patients and methods: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m2) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression. Results: Among the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0–47.0) years, median follow-up 22.0 (12.0–36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR [95%CI]: 0.28 [0.09–0.89], p = 0.032), high baseline serum creatinine (0.97 [0.95–0.99], p = 0.01) and high baseline proteinuria (0.37, [0.19–0.74], p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR [95%CI]: 6.2 [1.21–31.7], p = 0.029; 19.8 [2.01–186.7], p = 0.009, respectively) and having achieved PERR at 6 months (14.4 [3.28–63.6]; 11.7 [2.7–48.7], p = 0.001 for both). Conclusions: Add-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting.

Published
2021

35. Definition of fibromyalgia severity: Findings from a cross-sectional survey of 2339 Italian patients

Author

Salaffi, F., Di Carlo, M., Bazzichi, L., Atzeni, F., Govoni, M., Biasi, G., Di Franco, M., Mozzani, F., Gremese, E., Dagna, L., Batticciotto, A., Fischetti, F., Giacomelli, R., Guiducci, S., Guggino, G., Bentivegna, M., Gerli, R., Salvarani, C., Bajocchi, G., Ghini, M., Iannone, F., Giorgi, V., Farah, S., Cirillo, M., Bonazza, S., Barbagli, S., Gioia, C., Santilli, D., Capacci, A., Cavalli, G., Carubbi, F., Nacci, F., Riccucci, I., Sinigaglia, L., Masullo, M., Polizzi, B. M., Cutolo, M., Sarzi-Puttini, P., Gremese E. (ORCID:0000-0002-2248-1058), Bentivegna M., Santilli D., Cavalli G. (ORCID:0000-0003-1968-8987), Masullo M., Salaffi, F., Di Carlo, M., Bazzichi, L., Atzeni, F., Govoni, M., Biasi, G., Di Franco, M., Mozzani, F., Gremese, E., Dagna, L., Batticciotto, A., Fischetti, F., Giacomelli, R., Guiducci, S., Guggino, G., Bentivegna, M., Gerli, R., Salvarani, C., Bajocchi, G., Ghini, M., Iannone, F., Giorgi, V., Farah, S., Cirillo, M., Bonazza, S., Barbagli, S., Gioia, C., Santilli, D., Capacci, A., Cavalli, G., Carubbi, F., Nacci, F., Riccucci, I., Sinigaglia, L., Masullo, M., Polizzi, B. M., Cutolo, M., Sarzi-Puttini, P., Gremese E. (ORCID:0000-0002-2248-1058), Bentivegna M., Santilli D., Cavalli G. (ORCID:0000-0003-1968-8987), and Masullo M.

Abstract

Objective: To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods: Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: 'In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?'-which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results: The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th-75th percentiles) were respectively 61.16 (41.16-77.00), 27.00 (19.00-32.00) and 19.0 (13.00-24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0-23 for remission, 24-40 for mild disease, 41-63 for moderate disease, 64-82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0-12 for remission, 13-20 for mild disease, 21-28 for moderate disease, 29-33 for severe disease and >33 for very severe disease; PDS: 0-5 for remission, 6-15 for mild disease, 16-20 for moderate disease, 21-25 for severe disease and >25 for very severe disease. Conclusions: Disease severity cut-offs can represent an important improvement in interpreting FM.

Published
2021

36. Influence of the age at diagnosis in the disease expression of primary Sjögren's syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium

Author

Universitat Rovira i Virgili, Retamozo S; Acar-Denizli N; Horváth IF; Ng WF; Rasmussen A; Dong X; Li X; Baldini C; Olsson P; Priori R; Seror R; Gottenberg JE; Kruize AA; Hernandez-Molina G; Vissink A; Sandhya P; Armagan B; Quartuccio L; Sebastian A; Praprotnik S; Bartoloni E; Kwok SK; Kvarnstrom M; Rischmueller M; Soláns-Laqué R; Sene D; Pasoto SG; Suzuki Y; Isenberg DA; Valim V; Nordmark G; Nakamura H; Trevisani VFM; Hofauer B; Sisó-Almirall A; Giacomelli R; Devauchelle-Pensec V; Bombardieri M; Atzeni F; Hammenfors D; Maure B; Carsons SE; Gheita T; Sánchez-Berná I; López-Dupla M; Morel J; Inanç N; Fonseca-Aizpuru E; Morcillo C; Vollenweider C; Melchor S; Vázquez M; Díaz-Cuiza E; Consani-Fernández S; De-Miguel-Campo B; Szántó A; Bombardieri S; Gattamelata A; Hinrichs A; Sánchez-Guerrero J; Danda D; Kilic L; De Vita S; Wiland P; Gerli R; Park SH; Wahren-Herlenius M; Bootsma H; Mariette X; Ramos-Casals M; Brito-Zerón P, Universitat Rovira i Virgili, and Retamozo S; Acar-Denizli N; Horváth IF; Ng WF; Rasmussen A; Dong X; Li X; Baldini C; Olsson P; Priori R; Seror R; Gottenberg JE; Kruize AA; Hernandez-Molina G; Vissink A; Sandhya P; Armagan B; Quartuccio L; Sebastian A; Praprotnik S; Bartoloni E; Kwok SK; Kvarnstrom M; Rischmueller M; Soláns-Laqué R; Sene D; Pasoto SG; Suzuki Y; Isenberg DA; Valim V; Nordmark G; Nakamura H; Trevisani VFM; Hofauer B; Sisó-Almirall A; Giacomelli R; Devauchelle-Pensec V; Bombardieri M; Atzeni F; Hammenfors D; Maure B; Carsons SE; Gheita T; Sánchez-Berná I; López-Dupla M; Morel J; Inanç N; Fonseca-Aizpuru E; Morcillo C; Vollenweider C; Melchor S; Vázquez M; Díaz-Cuiza E; Consani-Fernández S; De-Miguel-Campo B; Szántó A; Bombardieri S; Gattamelata A; Hinrichs A; Sánchez-Guerrero J; Danda D; Kilic L; De Vita S; Wiland P; Gerli R; Park SH; Wahren-Herlenius M; Bootsma H; Mariette X; Ramos-Casals M; Brito-Zerón P

Abstract

Objective. To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). Methods. By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. Results. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.

Published
2021

38. AB0716 FIBROMYALGIA SYNDROME SEVERITY ACCORDING TO AGE CATEGORIES: RESULTS FROM A NATIONAL REGISTER

Author

Di Carlo, M., primary, Farah, S., additional, Bazzichi, L., additional, Atzeni, F., additional, Govoni, M., additional, Biasi, G., additional, DI Franco, M., additional, Mozzani, F., additional, Gremese, E., additional, Dagna, L., additional, Batticciotto, A., additional, Fischetti, F., additional, Giacomelli, R., additional, Guiducci, S., additional, Guggino, G., additional, Bentivegna, M., additional, Gerli, R., additional, Salvarani, C., additional, Bajocchi, G., additional, Ghini, M., additional, Iannone, F., additional, Giorgi, V., additional, Cirillo, M., additional, Bonazza, S., additional, Barbagli, S., additional, Gioia, C., additional, Marino, N. G., additional, Capacci, A., additional, Cavalli, G., additional, Cappelli, A., additional, Carubbi, F., additional, Nacci, F., additional, Ilenia, R., additional, Cutolo, M., additional, Sinigaglia, L., additional, Sarzi-Puttini, P., additional, and Salaffi, F., additional

Published
2021
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39. POS0693 EFFICACY AND SAFETY OF BELIMUMAB IN PATIENTS WITH LUPUS NEPHRITIS IN REAL-LIFE SETTING: RESULTS FROM A LARGE, NATIONWIDE, MULTICENTRIC, PROSPECTIVE COHORT

Author

Saccon, F., primary, Gatto, M., additional, Zen, M., additional, Fredi, M., additional, Regola, F., additional, Franceschini, F., additional, Tincani, A., additional, Emmi, G., additional, Ceccarelli, F., additional, Conti, F., additional, Bortoluzzi, A., additional, Govoni, M., additional, Mosca, M., additional, Tani, C., additional, Gerosa, M., additional, Ubiali, T., additional, Bozzolo, E., additional, Ramirez, G. A., additional, Moroni, L., additional, Gabrielli, A., additional, Cardinaletti, P., additional, Gremese, E., additional, Tanti, G., additional, De Vita, S., additional, De Marchi, G., additional, Fasano, S., additional, Ciccia, F., additional, Pazzola, G., additional, Salvarani, C., additional, Orsolini, G., additional, Rossini, M., additional, Faggioli, P., additional, Laria, A., additional, Scarpato, S., additional, De Paulis, A., additional, Brunetta, E., additional, Bartoloni Bocci, E., additional, Gerli, R., additional, Benvenuti, F., additional, Iaccarino, L., additional, and Doria, A., additional

Published
2021
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40. OP0310 GENDER AND FIBROMYALGIA SEVERITY: REAL LIFE DATA FROM THE ITALIAN REGISTRY

Author

Batticciotto, A., primary, Campanaro, F., additional, Atzeni, F., additional, Alciati, A., additional, DI Carlo, M., additional, Bazzichi, L., additional, Govoni, M., additional, Biasi, G., additional, DI Franco, M., additional, Mozzani, F., additional, Gremese, E., additional, Dagna, L., additional, Fischetti, F., additional, Giacomelli, R., additional, Guiducci, S., additional, Guggino, G., additional, Bentivegna, M., additional, Gerli, R., additional, Salvarani, C., additional, Bajocchi, G., additional, Ghini, M., additional, Iannone, F., additional, Giorgi, V., additional, Farah, S., additional, Bonazza, S., additional, Barbagli, S., additional, Gioia, C., additional, Capacci, A., additional, Cavalli, G., additional, Carubbi, F., additional, Nacci, F., additional, Ilenia, R., additional, Sinigaglia, L., additional, Cutolo, M., additional, Cappelli, A., additional, Sarzi-Puttini, P., additional, and Salaffi, F., additional

Published
2021
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43. Frequency and clinical correlates of antiphospholipid antibodies arising in patients with SARS-CoV-2 infection: findings from a multicentre study on 122 cases

Author

MARIELE GATTO, Perricone, C., Tonello, M., Bistoni, O., Cattelan, A. M., Bursi, R., Cafaro, G., Robertis, E., Mencacci, A., Bozza, S., Vianello, A., Iaccarino, L., Gerli, R., Doria, A., and Bartoloni, E.

Subjects
SARS-CoV-2, Pneumonia, Viral, COVID-19, Anticardiolipin, Thrombosis, Antiphospholipid, Pneumonia, Antiphospholipid Syndrome, Antibodies, Betacoronavirus, Immunoglobulin M, beta 2-Glycoprotein I, Antibodies, Anticardiolipin, Immunoglobulin G, Antibodies, Antiphospholipid, Humans, Viral, Coronavirus Infections, Pandemics
Abstract

COVID-19 features include disseminated intravascular coagulation and thrombotic microangiopathy indicating a hypercoagulable state. We aimed to investigate antiphospholipid antibodies (aPL) prevalence and clinical relationships in a large cohort of COVID-19 patients.We analysed the prevalence and titres of serum aPL in 122 patients with COVID-19 and 157 with primary antiphospholipid syndrome (PAPS) and 91 with other autoimmune rheumatic diseases (oARD) for comparison. IgG/IgM anticardiolipin (aCL) and IgG/IgM anti-beta2glycoprotein I (β2GPI) were assayed using homemade ELISA, IgA aCL and anti-β2GPI by commercial ELISA kits and lupus anticoagulant (LAC) by multiple coagulation tests following updated international guidelines.Prevalence of IgG and IgM aCL and of IgG and IgM anti-β2GPI across COVID-19 patients were 13.4%, 2.7%, 6.3% and 7.1%, being significantly lower than in PAPS (p0.0001 for all). Frequency of IgG aCL and IgM anti-β2GPI was comparable to oARD (13.4% vs. 13.2% and 7.1% vs. 11%, respectively), while IgG anti-β2GPI and IgM aCL were lower (p0.01). IgA aCL and IgA anti-β2GPI were retrieved in 1.7% and 3.3% of COVID-19 patients, respectively. Positive LAC was observed in 22.2% COVID-19 vs. 54.1% of PAPS (p0.0001) and 14.6% of oARD (p=0.21). Venous or arterial thromboses occurred in 18/46 (39.1%) COVID-19 patients and were not associated with positive aPL (p=0.09).Thrombosis is a frequent manifestation during COVID-19 infection. However, prevalence and titres of aPL antibodies or LAC were neither consistently increased nor associated with thrombosis when measured at a single timepoint, therefore not representing a suitable screening tool in the acute stage of disease.

Published
2020

45. Validation of thymic stromal lymphopoietin as a biomarker of primary Sjögren's syndrome and related lymphoproliferation: results in independent cohorts

Author

Saviana Gandolfo, Fabro, C., Kapsogeorgou, E., Colafrancesco, S., Ferro, F., Bartoloni, E., Quartuccio, L., Goules, A., Priori, R., Alunno, A., Conti, F., Valesini, G., Giacomelli, R., Baldini, C., Gerli, R., Tzioufas, A. G., and Vita, S.

Subjects
Biomarkers, Cytokines, Greece, Humans, Italy, Sjogren's Syndrome, Thymic Stromal Lymphopoietin, sjogren's syndrome, thymic stromal lymphopoietin, biomarkers, lymphoma, mucosa-associated lymphoid tissue
Abstract

Thymic stromal lymphopoietin (TSLP) has been implicated in primary Sjögren's syndrome (pSS) and related B-cell lymphoproliferation and lymphoma (NHL) by studies on salivary pathologic tissues and serum. The purpose of this work was to validate serum TSLP as biomarker of pSS and related lymphoproliferation by the study of two additional independent cohorts.Serum TSLP was measured by ELISA in the original published Cohort-1 from Udine, Italy, including 91 patients. Two additional cohorts were then studied for validation: Cohort-2, including 4 sub-cohorts comprising 125 patients from the Universities of Roma, L'Aquila, Pisa and Perugia, belonging to the Italian SS Study Group (GRISS), and Cohort-3, including 59 patients from the University of Athens, Greece. Overall, 159 control subjects were enrolled. Active pSS-NHL, as well as pre-lymphomatous conditions, i.e. persistent salivary gland swelling and mixed cryoglobulinaemia, were investigated in detail. In addition, serum samples from pSS-NHL in complete remission were analysed (n=27).TSLP serum levels were confirmed to be significantly higher in pSS compared to controls in both Cohort-2 and Cohort-3, in particular in patients with lymphoproliferation. Serum TSLP was much higher in pSS pre-lymphomatous conditions. Finally, active NHL showed the highest TSLP serum levels, while in NHL in remission TSLP resulted undetectable or significantly lower than in benign pSS.By the study of independent cohorts, it was again demonstrated that serum TSLP levels are increased in pSS, above all in more advanced B-cell lymphoproliferation and NHL. Serum TSLP can therefore represent a novel biomarker for pSS-related lymphoproliferation.

Published
2020

47. Significance of anti-La/SSB antibodies in primary Sjögren's syndrome patients with combined positivity for anti-Ro/SSA and salivary gland biopsy

Author

Cafaro, G., Perricone, C., Baldini, C., Luca Quartuccio, Priori, R., Carubbi, F., Ferro, F., Colafrancesco, S., Bini, V., Vita, S., Giacomelli, R., Gerli, R., and Bartoloni, E.

Subjects
autoantibodies, Biopsy, lymphoma, anti-La/SSB, Antibodies, Salivary Glands, Sjogren's Syndrome, anti-Ro/SSA, salivary gland biopsy, Antibodies, Antinuclear, Antinuclear, Sjogren's syndrome, autoimmune diseases, Humans, Retrospective Studies
Abstract

Immunological parameters exert a relevant diagnostic and prognostic role in primary Sjögren's syndrome (pSS) and may identify specific disease phenotypes. Among disease-associated immunological features, anti-La/SSB are rarely found without concomitant anti-Ro/SSA and their clinical significance in patients with pSS has been poorly investigated. Thus, we aimed to characterise the value of anti-La/SSB analysing clinical and serologic features of a wide cohort of pSS patients with both circulating anti-Ro/SSA and positive salivary gland biopsy (SGB).Clinical and serological data of 600 pSS patients with both anti-Ro/SSA and SGB positivity and categorised according to anti-La/SSB status were retrospectively analysed. Comparisons between patients with and without circulating anti-La/SSB were performed.Among the whole cohort, 319 (53%) of patients were anti-La/SSB negative and 281 (47%) were anti-La/SSB positive. Anti-La/SSB positive patients were younger at disease diagnosis and had a longer disease duration. Moreover, anti-La/SSB positive patients had a higher prevalence of hypergammaglobulinaemia and circulating rheumatoid factor and of lymphoproliferative disorders in comparison to seronegative group. At multivariate analysis, hypergammaglobulinaemia (OR=1,7; 95% CI 1.17, 2.43), rheumatoid factor (OR=2.3; 95% CI 1.6, 3.3) and lymphoma (OR=2.6; 95% CI 1.12, 5.96) were identified as independent variables significantly associated with anti-La/SSB positivity.In patients with pSS and concomitant anti-Ro/SSA and SGB positivity, the presence of anti-La/SSB may help in identifying a disease subset with distinct prognostic features, especially in terms of higher risk of lymphoproliferative complications.

Published
2020

48. Erratum. management of adult-onset still's disease with interleukin-1 inhibitors. evidence- and consensus-based statements by a panel of Italian experts

Author

Colafrancesco, S., Manara, M., Bortoluzzi, A., Serban, T., Bianchi, G., Cantarini, L., Ciccia, F., Dagna, L., Govoni, M., Montecucco, C., Priori, R., Ravelli, A., Sfriso, P., Sinigaglia, L., Alivernini, S., Baldissera, E., Bartoloni, E., Berti, A., Bugatti, S., Camellino, D., Cammelli, D., Caporali, R., Caso, F., Cavallaro, E., Cavalli, G., Colaci, M., Costa, L., Di Scala, G., Emmi, G., Frassi, M., Gerli, R., Giacomelli, R., Gremese, E., Iannone, F., Lapadula, G., Leveghi, L., Lopalco, G., Manna, R., Marotto, D., Mathieu, A., Neri, R., Patisso, I., Piga, M., Punzi, L., Romano, M., Ruscitti, P., Salvarani, C., Scarpa, R., Scrivo, R., Talarico, R., Verrecchia, E., Viapiana, O., Vitale, A., and Vitiello, G.

Subjects
030203 arthritis & rheumatology, 0301 basic medicine, medicine.medical_specialty, Pediatrics, Adult-onset Still's disease, lcsh:Diseases of the musculoskeletal system, business.industry, Published Erratum, MEDLINE, Interleukin, Rheumatology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, medicine, lcsh:RC925-935, business
Abstract

Following publication of the original article [1], it was brought to our attention that the AOSD Consensus Group was incorrectly tagged and therefore not searchable. The publishers apologize for this error.

Published
2020

49. The differential response to anti IL-6 treatment in COVID-19: the genetic counterpart

Author

Perricone C, Conigliaro P, Ciccacci C, Marcucci E, Giacomo Cafaro, Bartoloni E, Perricone R, Novelli G, Borgiani P, and Gerli R

Subjects
Antigens, Differentiation, T-Lymphocyte, Pneumonia, Viral, Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, Antibodies, Arthritis, Rheumatoid, Betacoronavirus, Antigens, CD, Rheumatoid, Lectins, Monoclonal, Receptors, 80 and over, Humans, Lectins, C-Type, Viral, Antigens, Polymorphism, Pandemics, Humanized, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, C-Type, SARS-CoV-2, Interleukin-6, Arthritis, Signal Transducing, COVID-19, Adaptor Proteins, Pneumonia, Single Nucleotide, Middle Aged, Receptors, Interleukin-6, CD, T-Lymphocyte, Settore MED/03, Differentiation, Coronavirus Infections
Published
2020

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