43 results on '"Biagioli T"'
Search Results
2. Two‐site evaluation of the diagnostic performance of the Sysmex XN Body Fluid (BF) module for cell count and differential in Cerebrospinal Fluid
- Author
-
Buoro, S., Peruzzi, B., Fanelli, A., Seghezzi, M., Manenti, B., Lorubbio, M., Biagioli, T., Nannini, S., Ottomano, C., and Lippi, G.
- Published
- 2018
- Full Text
- View/download PDF
3. MSCs-DCs interaction: a cell-cell contact mechanism inducing tolerance: O164
- Author
-
Aldinucci, A., Biagioli, T., Pieri, L., Romagnoli, P., Mazzanti, B., Saccardi, R., Massacesi, L., and Ballerini, C.
- Published
- 2009
4. Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis
- Author
-
Cavaletti, G, Cavalletti, E, Crippa, L, Di Luccio, E, Oggioni, N, Mazzanti, B, Biagioli, T, Sala, F, Sala, V, Frigo, M, Rota, S, Tagliabue, E, Stanzani, L, Galbiati, S, Rigolio, R, Zoia, C, Tredici, G, Perseghin, P, Dassi, M, Riccio, P, and Lolli, F
- Published
- 2004
- Full Text
- View/download PDF
5. CEREBROSPINAL FLUID T-REGULATORY CELLS RECOGNIZE BORRELIA BURGDORFERI NAPA IN CHRONIC LYME BORRELIOSIS.
- Author
-
AMEDEI, A., CODOLO, G., OZOLINS, D., BALLERINI, C., BIAGIOLI, T., JAUNALKSNE, I., ZILEVICA, A., D'ELIOS, S., DE BERNARD, M., and D'ELIOS, M. M.
- Published
- 2013
- Full Text
- View/download PDF
6. HPLC and flow cytometry combined approach for HbF analysis in fetomaternal haemorrhage evaluation.
- Author
-
Peruzzi B, Guerrieri S, Biagioli T, Lanzilao L, Pratesi S, Bencini S, Statello M, Carraresi A, Stefanelli S, Tonelli M, Brogi M, Capone M, Mazzoni A, Gelli AMG, Fanelli A, Caporale R, and Annunziato F
- Abstract
Introduction: Recently, a flow cytometric (FC) based test has been developed for detection of circulating fetal cells to replace the less accurate and reproducible Kleihauer-Betke test.FC test is easier to perform, it can distinguish the origin of fetal cells, but it is expensive and available in highly specialized laboratories. We evaluated the introduction of high-performance liquid chromatography (HPLC) approach as initial screening to identify patients who need an additional FC test to better discriminate the nature of haemoglobin-F (HbF) positive cells., Methods: Blood samples from 130 pregnant women suspected to have fetomaternal haemorrhage were analysed with HPLC and FC methods. The cut-off for HbF HPLC concentration was calculated. Statistical analyses for the evaluation of HPLC as a screening method were performed. The positivity cut-off of HbF to be used as decision-making value to continue the investigation was calculated., Results: An excellent agreement (R
2 > 0.90) was observed between the percentage of HbF obtained by HPLC and the percentage of fetal cells detected by FC. Results obtained from each assay were compared to define the HPLC threshold below which it is not necessary to continue the investigations, confirming the maternal nature of the HbF positive cells detected. Our study demonstrated that a cut-off of 1.0 % HbF obtained by HPLC was associated with the lowest rate of false negative results in our patient cohort., Conclusions: This study provides a new FMH investigation approach that possibly leads to a reduction in times and costs of the analysis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF
7. Biomarkers of traumatic brain injury in vitreous humor: A pilot study.
- Author
-
Lanzilao L, Bianchi I, Grassi S, Defraia B, Brogi M, Da Ros M, Biagioli T, Fanelli A, Pinchi V, and Focardi M
- Subjects
- Humans, Pilot Projects, S100 Calcium Binding Protein beta Subunit, Biomarkers, Glial Fibrillary Acidic Protein, Ferritins, Vitreous Body, Brain Injuries, Traumatic diagnosis
- Abstract
Background: Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality worldwide. The patients' and injuries' heterogeneity associated with TBI, alongside with its variable clinical manifestations, make it challenging to make diagnosis and predict prognosis. Therefore, the identification of reliable prognostic markers would be relevant both to support clinical decision-making and forensic evaluation of polytraumatic deaths and cases of medical malpractice. This pilot study aimed to evaluate some of the main biomarkers specific for brain damage in sTBI and mmTBI deaths in samples of vitreous humor (VH) in order to verify whether predictors of prognosis in TBI can be found in this matrix., Methods: VH were obtained from both eyes (right and left) of 30 cadavers (20 sTBI and 10 mmTBI) and analysed. These factors were evaluated: NSE (neuron-specific enolase), S100 calcium-binding protein (S100), glial fibrillary acidic protein (GFAP), Brain-derived neurotrophic factor (BDNF), Copeptin, Interleukin 6 (IL-6), Ferritin, Lactate dehydrogenase (LDH), C-Reactive Protein (CRP), Procalcitonin (PCT), Glucose and Neutrophil gelatinase-associated lipocalin (N-Gal)., Results: Four of the analysed proteins (LDH, ferritin, S100 and NSE) proved to be particularly promising. In particular, logistic regression analysis found a good discriminatory power., Conclusions: Given the peculiarity of the matrix and the poor standardization of the sampling, such promising results need to be furtherly investigated in serum before being implemented in the forensic practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
8. The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study.
- Author
-
Bernardi G, Biagioli T, Malpassi P, De Michele T, Vecchio D, Repice AM, Lugaresi A, Mirabella M, Torri Clerici V, and Crespi I
- Subjects
- Biomarkers, Humans, Immunoglobulin kappa-Chains, Oligoclonal Bands cerebrospinal fluid, ROC Curve, Multiple Sclerosis, Nervous System Diseases
- Abstract
Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus., Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases., Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite., Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index., Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.
- Published
- 2022
- Full Text
- View/download PDF
9. Intermediate-Intensity Autologous Hematopoietic Stem Cell Transplantation Reduces Serum Neurofilament Light Chains and Brain Atrophy in Aggressive Multiple Sclerosis.
- Author
-
Mariottini A, Marchi L, Innocenti C, Di Cristinzi M, Pasca M, Filippini S, Barilaro A, Mechi C, Fani A, Mazzanti B, Biagioli T, Materozzi F, Saccardi R, Massacesi L, and Repice AM
- Abstract
Background: Autologous haematopoietic stem cell transplantation (AHSCT) is highly effective in reducing new inflammatory activity in aggressive multiple sclerosis (MS). A remarkable decrease of serum neurofilament light chains (sNfL) concentration, a marker of axonal damage, was reported in MS following high-intensity regimen AHSCT, but hints for potential neurotoxicity had emerged. sNfL and brain atrophy were therefore analysed in a cohort of patients with aggressive MS treated with intermediate-intensity AHSCT, exploring whether sNfL might be a reliable marker of disability progression independent from new inflammation (i.e. relapses and/or new/gadolinium-enhancing MRI focal lesions)., Methods: sNfL concentrations were measured using SIMOA methodology in peripheral blood from relapsing-remitting (RR-) or secondary-progressive (SP-) MS patients undergoing AHSCT (MS AHSCT), collected before transplant and at months 6 and 24 following the procedure. sNfL measured at a single timepoint in SP-MS patients not treated with AHSCT without recent inflammatory activity (SP-MS CTRL) and healthy subjects (HD) were used as controls. The rate of brain volume loss (AR-BVL) was also evaluated by MRI in MS AHSCT cases., Results: Thirty-eight MS AHSCT (28 RR-MS; 10 SP-MS), 22 SP-MS CTRL and 19 HD were included. Baseline median sNfL concentrations were remarkably higher in the MS AHSCT than in the SP-MS CTRL and HD groups ( p = 0.005 and <0.0001, respectively), and levels correlated with recent inflammatory activity. After a marginal (not significant) median increase observed at month 6, at month 24 following AHSCT sNfL concentrations decreased compared to baseline by median 42.8 pg/mL (range 2.4-217.3; p = 0.039), reducing by at least 50% in 13 cases, and did not differ from SP-MS CTRL ( p = 0.110) but were still higher than in HD ( p < 0.0001). Post-AHSCT AR-BVL normalised in 55% of RR-MS and in 30% of SP-MS. The effectiveness and safety of AHSCT were aligned with the literature., Conclusion: sNfL concentrations correlated with recent inflammatory activity and were massively and persistently reduced by intermediate-intensity AHSCT. Association with response to treatment assessed by clinical or MRI outcomes was not observed, suggesting a good sensitivity of sNfL for recent inflammatory activity but low sensitivity in detecting ongoing axonal damage independent from new focal inflammation., 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 Mariottini, Marchi, Innocenti, Di Cristinzi, Pasca, Filippini, Barilaro, Mechi, Fani, Mazzanti, Biagioli, Materozzi, Saccardi, Massacesi and Repice.)
- Published
- 2022
- Full Text
- View/download PDF
10. Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis.
- Author
-
Fonderico M, Portaccio E, Razzolini L, Pastò L, Bellinvia A, Addazio I, Betti M, Aprea MG, Ballerini C, Biagioli T, and Amato MP
- Abstract
The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.
- Published
- 2021
- Full Text
- View/download PDF
11. TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood.
- Author
-
Amoriello R, Chernigovskaya M, Greiff V, Carnasciali A, Massacesi L, Barilaro A, Repice AM, Biagioli T, Aldinucci A, Muraro PA, Laplaud DA, Lossius A, and Ballerini C
- Subjects
- Adult, Aged, Blood-Brain Barrier, Case-Control Studies, Female, High-Throughput Nucleotide Sequencing, Humans, Italy, Male, Middle Aged, Multiple Sclerosis cerebrospinal fluid, Multiple Sclerosis genetics, Receptors, Antigen, T-Cell blood, Receptors, Antigen, T-Cell genetics, Sequence Analysis, DNA, Young Adult, Cerebrospinal Fluid immunology, Computational Biology methods, Multiple Sclerosis immunology, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes immunology
- Abstract
Background: T cells play a key role in the pathogenesis of multiple sclerosis (MS), a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Although several studies recently investigated the T-cell receptor (TCR) repertoire in cerebrospinal fluid (CSF) of MS patients by high-throughput sequencing (HTS), a deep analysis on repertoire similarities and differences among compartments is still missing., Methods: We performed comprehensive bioinformatics on high-dimensional TCR Vβ sequencing data from published and unpublished MS and healthy donors (HD) studies. We evaluated repertoire polarization, clone distribution, shared CDR3 amino acid sequences (CDR3s-a.a.) across repertoires, clone overlap with public databases, and TCR similarity architecture., Findings: CSF repertoires showed a significantly higher public clones percentage and sequence similarity compared to peripheral blood (PB). On the other hand, we failed to reject the null hypothesis that the repertoire polarization is the same between CSF and PB. One Primary-Progressive MS (PPMS) CSF repertoire differed from the others in terms of TCR similarity architecture. Cluster analysis splits MS from HD., Interpretation: In MS patients, the presence of a physiological barrier, the blood-brain barrier, does not impact clone prevalence and distribution, but impacts public clones, indicating CSF as a more private site. We reported a high Vβ sequence similarity in the CSF-TCR architecture in one PPMS. If confirmed it may be an interesting insight into MS progressive inflammatory mechanisms. The clustering of MS repertoires from HD suggests that disease shapes the TCR Vβ clonal profile., Funding: This study was partly financially supported by the Italian Multiple Sclerosis Foundation (FISM), that contributed to Ballerini-DB data collection (grant #2015 R02)., Competing Interests: Declaration of Competing Interest A.L. reports grants from Sanofi Genzyme, outside the submitted work. D.L. reports grants from EDMUS Foundation, from ARSEP Foundation and from ANR, and personal fees from Biogen, BMS, Alexion, Merck, Sanofi and Roche, outside the submitted work. P.A.M. reports personal fees from Jasper Therapeutics and from Magenta Therapeutics, outside the submitted work. V.G. declares advisory board positions in aiNET GmbH and Enpicom B.V., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
12. Prognostic role of intrathecal IgM synthesis in multiple sclerosis: Results from a clinical series.
- Author
-
Fonderico M, Biagioli T, Lanzilao L, Bellinvia A, Fratangelo R, Pastò L, Prestipino E, Razzolini L, Tudisco L, Ginestroni A, Vuolo L, Fainardi E, Ballerini C, Portaccio E, and Amato MP
- Subjects
- Disease Progression, Humans, Immunoglobulin M, Magnetic Resonance Imaging, Oligoclonal Bands, Prognosis, Retrospective Studies, Multiple Sclerosis diagnostic imaging
- Abstract
Background: There is emerging evidence that intrathecal IgM synthesis (ITMS) is a risk factor for conversion to clinically defined multiple sclerosis (CDMS) in clinically isolated syndrome (CIS) patients., Objectives: The objective of this study is to verify the prognostic role of ITMS as a risk factor for the second clinical attack in patients after the first demyelinating event., Methods: Monocentric observational study performed on prospectively acquired clinical data and retrospective evaluation of magnetic resonance imaging (MRI) data. ITMS was assessed according to Reiber's non-linear function. We compared time to the second attack by using Kaplan-Meier curves and performed adjustment by Cox regression analysis., Results: Demographics and clinical data were collected prospectively in a cohort of 68 patients. ITMS occurred in 40% (27/68) of patients who had a higher T1-hypointense lesion load at brain MRI ( p = 0.041). In multivariate Cox regression analysis (adjusted for age, sex, baseline Expanded Disability Status Scale, IgG oligoclonal bands and disease-modifying treatment exposure), relapsing-remitting multiple sclerosis (MS) patients with ITMS were at higher risk to experience a second clinical attack (adjusted hazard ratio (aHR) = 6.3, 95% confidence interval (CI) = 2.1-18.4, p = 0.001)., Conclusion: Together with previous studies, our findings support the role of ITMS as a prognostic biomarker in MS.
- Published
- 2021
- Full Text
- View/download PDF
13. Anti-MAG IgM: differences in antibody tests and correlation with clinical findings.
- Author
-
Matà S, Ambrosini S, Saccomanno D, Biagioli T, Carpo M, Amantini A, Giannini F, Barilaro A, Toscani L, Del Mastio M, Comi GP, and Sorbi S
- Subjects
- Adolescent, Animals, Child, Child, Preschool, Female, Humans, Male, Myelin Sheath immunology, Myelin-Associated Glycoprotein immunology, Peripheral Nervous System Diseases drug therapy, Polyneuropathies immunology, Rats, Young Adult, Autoantibodies blood, Immunoglobulin M immunology, Myelin-Associated Glycoprotein metabolism, Peripheral Nervous System Diseases immunology
- Abstract
Objectives: Anti-myelin-associated glycoprotein (MAG) antibody is associated with clinically heterogeneous polyneuropathies. Our purpose was to compare neuropathy phenotypes identified by different anti-MAG tests' results., Methods: Cohort study: Sera from 40 neuropathy anti-MAG EIA positive patients were tested for anti-MAG by Western blot (WB), for anti-peripheral nerve myelin (PNM) on monkey nerve by immunofluorescence assay (IFA), and for anti-HNK1 on rat CNS slices by IFA. Anti-sulfatide antibodies, for comparison, were also tested by EIA., Results: Among 40 anti-MAG EIA positive sera, 85% also had anti-PNM IFA reactivity and 67.5% bind HNK1 on rat CNS. Anti-HNK1 positive patients had the classical predominantly distal acquired demyelinating symmetric (DADS) neuropathy with a benign course, while anti-PNM positive but anti-HNK1 negative patients had predominantly axonal neuropathy with a high frequency of anti-sulfatide reactivity and the worst long-term prognosis. Anti-MAG EIA positive patients without anti-PNM or anti-HNK1 IFA reactivity had a CIDP-like polyneuropathy., Conclusion: Different methods to test for anti-MAG antibodies identify different clinical and electrophysiological findings, as well as long-term outcome. HNK1 reactivity is the strongest marker of DADS.
- Published
- 2020
- Full Text
- View/download PDF
14. Anti-ganglioside antibodies: experience from the Italian Association of Neuroimmunology external quality assessment scheme.
- Author
-
Franciotta D, Gastaldi M, Biagioli T, Benedetti L, Giannotta C, Bedin R, Zardini E, and Nobile-Orazio E
- Subjects
- Enzyme-Linked Immunosorbent Assay standards, Humans, Italy, Laboratories standards, Quality Control, Autoantibodies blood, Autoimmune Diseases diagnosis, Enzyme-Linked Immunosorbent Assay methods, Gangliosides immunology
- Abstract
Background Anti-ganglioside antibodies are currently used in the differential diagnosis of suspected immune-mediated neuropathies. In-house and increasingly used commercial assays seem to perform suboptimally, and comparative information on their analytical performance are essentially lacking. Born within the frame of guidelines and standardization activities by the Italian Association of Neuroimmunology, this external quality assessment scheme (EQAS) is a real-life snapshot of the laboratory diagnostics in this field. Methods The EQAS consisted of five surplus, anonymized serum samples from patients with clinically-defined neuropathies and two serum samples from healthy blood donors. Eight laboratories used commercial line-/dot-blots, seven in-house/commercial ELISAs (in addition, 13 laboratories tested a recently released ELISA by Bühlmann). Only high anti-ganglioside antibody reactivities were considered, in accordance with consolidated recommendations. Results Large variations in anti-ganglioside antibody profiles were observed, even, although to a lesser extent, within homogeneous classes of assays. Concordance between the profiles and clinical phenotypes was also partial. Conclusions Although conducted on a relatively small, but representative number of Italian laboratories, this EQAS shows a critical between-laboratory disagreement in the test results of anti-ganglioside antibodies. Also considering the trend for using certified assays in generalist laboratories, strong efforts toward standardization and the identification of the best method(s) for their determinations are compellingly needed.
- Published
- 2018
- Full Text
- View/download PDF
15. CSF/serum matrix metallopeptidase-9 ratio discriminates neuro Behçet from multiple sclerosis.
- Author
-
Aldinucci A, Bonechi E, Biagioli T, Repice AM, D'Elios MM, Emmi L, Emmi G, Silvestri E, Barilaro A, and Ballerini C
- Abstract
In neuro Behçet disease with multiple sclerosis-like features, diagnosis could be challenging. Here, we studied the cerebrospinal fluid and serum inflammatory profile of 11 neuro Behçet and 21 relapsing-remitting multiple sclerosis patients. Between the soluble factors analyzed (MMP9, TNF α , IL6, CXCL13, CXCL10, CXCL8, IFN γ , IL10, IL17, IL23, and others) we found MMP9 increased in neuro Behçet serum compared to multiple sclerosis and decreased in cerebrospinal fluid. Furthermore, neuro Behçet analysis of circulating natural killer CD56
DIM subset suggests their potential involvement in increased MMP9 production. We believe that these findings may have a translational utility in clinical practice.- Published
- 2018
- Full Text
- View/download PDF
16. Diagnostics of anti-MAG antibody polyneuropathy.
- Author
-
Franciotta D, Gastaldi M, Benedetti L, Garnero M, Biagioli T, Brogi M, Costa G, Fadda E, Andreetta F, Simoncini O, Giannotta C, Bazzigaluppi E, Fazio R, Bedin R, Ferraro D, Mariotto S, Ferrari S, Galloni E, De Riva V, Zardini E, Cortese A, and Nobile-Orazio E
- Subjects
- Humans, Polyneuropathies immunology, Autoantibodies, Myelin-Associated Glycoprotein immunology, Polyneuropathies diagnosis
- Abstract
This document presents the guidelines for anti-myelin-associated glycoprotein (MAG) antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of sponsoring Italian Association of Neuroimmunology (AINI) congresses. The main clinical information on anti-MAG antibody polyneuropathy, indications and limits of anti-MAG antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
- Published
- 2017
- Full Text
- View/download PDF
17. Cerebrospinal fluid analysis and the determination of oligoclonal bands.
- Author
-
Gastaldi M, Zardini E, Leante R, Ruggieri M, Costa G, Cocco E, De Luca G, Cataldo I, Biagioli T, Ballerini C, Castellazzi M, Fainardi E, Pettini P, Zaffaroni M, Giunti D, Capello E, Bernardi G, Ciusani E, Giannotta C, Nobile-Orazio E, Bazzigaluppi E, Passerini G, Bedin R, Sola P, Brivio R, Cavaletti G, Sala A, Bertolotto A, Desina G, Leone MA, Mariotto S, Ferrari S, Paternoster A, Giavarina D, Lolli F, and Franciotta D
- Subjects
- Humans, Oligoclonal Bands analysis, Demyelinating Autoimmune Diseases, CNS cerebrospinal fluid, Demyelinating Autoimmune Diseases, CNS immunology, Oligoclonal Bands cerebrospinal fluid
- Abstract
This document presents the guidelines for the cerebrospinal fluid (CSF) analysis and the determination of oligoclonal bands (OCBs) as pivotal tests in neuroinflammatory pathologies of the central nervous system. The guidelines have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on the pathologies in which the CSF analysis is indicated, and, particularly, on those characterized by the presence of OCBs in the intrathecal compartment, indications and limits of CSF analysis and OCB determination, instructions for result interpretation, and agreed laboratory protocols (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
- Published
- 2017
- Full Text
- View/download PDF
18. Diagnostics of paraneoplastic neurological syndromes.
- Author
-
Zoccarato M, Gastaldi M, Zuliani L, Biagioli T, Brogi M, Bernardi G, Corsini E, Bazzigaluppi E, Fazio R, Giannotta C, Nobile-Orazio E, Costa G, Iorio R, Evoli A, Mariotto S, Ferrari S, Galloni E, De Riva V, Zardini E, Franciotta D, and Giometto B
- Subjects
- Autoantibodies immunology, Autoantibodies metabolism, Humans, Paraneoplastic Syndromes, Nervous System immunology, Paraneoplastic Syndromes, Nervous System metabolism, Paraneoplastic Syndromes, Nervous System diagnosis
- Abstract
This document presents the guidelines for onconeural antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on paraneoplastic neurological syndromes, indications and limits of onconeural antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
- Published
- 2017
- Full Text
- View/download PDF
19. Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD).
- Author
-
Franciotta D, Gastaldi M, Sala A, Andreetta F, Rinaldi E, Ruggieri M, Leante R, Costa G, Biagioli T, Massacesi L, Bazzigaluppi E, Fazio R, Mariotto S, Ferrari S, Galloni E, Perini F, Zardini E, Zuliani L, Zoccarato M, Giometto B, and Bertolotto A
- Subjects
- Antibodies metabolism, Humans, Neuromyelitis Optica immunology, Aquaporin 4 immunology, Neuromyelitis Optica diagnosis
- Abstract
This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
- Published
- 2017
- Full Text
- View/download PDF
20. Diagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens.
- Author
-
Zuliani L, Zoccarato M, Gastaldi M, Iorio R, Evoli A, Biagioli T, Casagrande S, Bazzigaluppi E, Fazio R, Giannotta C, Nobile-Orazio E, Andreetta F, Simoncini O, Costa G, Mariotto S, Ferrari S, Galloni E, Marcon M, Franciotta D, and Giometto B
- Subjects
- Humans, Models, Molecular, Antibodies metabolism, Antigens, Surface immunology, Encephalitis diagnosis, Hashimoto Disease diagnosis, Nerve Tissue Proteins immunology
- Abstract
This document presents the guidelines for testing antibodies against neuronal surface antigens that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on autoimmune encephalitis associated with antibodies against neuronal surface antigens, indications and limits of testing for such antibodies, instructions for result interpretation, and an agreed laboratory protocol (Appendix A) are reported for the communicative community of neurologists and clinical pathologists.
- Published
- 2017
- Full Text
- View/download PDF
21. Diagnostics of dysimmune peripheral neuropathies.
- Author
-
Franciotta D, Gastaldi M, Benedetti L, Pesce G, Biagioli T, Lolli F, Costa G, Melis C, Andreetta F, Simoncini O, Giannotta C, Bazzigaluppi E, Fazio R, Bedin R, Ferraro D, Mariotto S, Ferrari S, Galloni E, De Riva V, Zardini E, Cortese A, and Nobile-Orazio E
- Subjects
- Antibodies metabolism, Autoimmune Diseases of the Nervous System complications, Gangliosides immunology, Humans, Peripheral Nervous System Diseases complications, Autoimmune Diseases of the Nervous System diagnosis, Peripheral Nervous System Diseases diagnosis
- Abstract
This document presents the guidelines for anti-ganglioside antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Main clinical information on dysimmune peripheral neuropathies, indications and limits of anti-ganglioside antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
- Published
- 2017
- Full Text
- View/download PDF
22. Proposal for a New Score-Based Approach To Improve Efficiency of Diagnostic Laboratory Workflow for Acute Bacterial Meningitis in Adults.
- Author
-
Lagi F, Bartalesi F, Pecile P, Biagioli T, Caldini AL, Fanelli A, Giannazzo G, Grifoni S, Massacesi L, Bartoloni A, and Rossolini GM
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Cells, Cerebrospinal Fluid chemistry, Cerebrospinal Fluid cytology, Female, Humans, Italy, Leukocyte Count, Male, Middle Aged, Retrospective Studies, Young Adult, Clinical Laboratory Techniques methods, Decision Support Techniques, Diagnostic Tests, Routine methods, Meningitis, Bacterial diagnosis, Workflow
- Abstract
Microbiological tests on cerebrospinal fluid (CSF) utilize a common urgent-care procedure that does not take into account the chemical and cytological characteristics of the CSF, resulting sometimes in an unnecessary use of human and diagnostic resources. The aim of this study was to retrospectively validate a simple scoring system (bacterial meningitis-Careggi score [BM-CASCO]) based on blood and CSF sample chemical/cytological parameters for evaluating the probability of acute bacterial meningitis (ABM) in adults. BM-CASCO (range, 0 to 6) was defined by the following parameters: CSF cell count, CSF protein levels, CSF lactate levels, CSF glucose-to-serum glucose ratio, and peripheral neutrophil count. BM-CASCO was retrospectively calculated for 784 cases of suspected ABM in adult subjects observed during a four-and-a-half-year-period (2010 to 2014) at the emergency department (ED) of a large tertiary-care teaching hospital in Italy. Among the 28 confirmed ABM cases (3.5%), Streptococcus pneumoniae was the most frequent cause (16 cases). All ABM cases showed a BM-CASCO value of ≥3. Most negative cases (591/756) exhibited a BM-CASCO value of ≤1, which was adopted in our laboratory as a cutoff to not proceed with urgent microbiological analysis of CSF in cases of suspected ABM in adults. During a subsequent 1-year follow-up, the introduction of the BM-CASCO in the diagnostic workflow of ABM in adults resulted in a significant decrease in unnecessary microbiological analysis, with no false negatives. In conclusion, BM-CASCO appears to be an accurate and simple scoring system for optimization of the microbiological diagnostic workflow of ABM in adults., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
- Full Text
- View/download PDF
23. New patterns of relapse in multiple myeloma: a case of "light chain escape" in which FLC predicted relapse earlier than urine and serum immunofixation.
- Author
-
Caldini A, Nozzoli C, Terreni A, Staderini M, Berardi M, Biagioli T, Brogi M, and Bosi A
- Subjects
- Bence Jones Protein urine, Bendamustine Hydrochloride therapeutic use, Blood Protein Electrophoresis, Bortezomib therapeutic use, Dexamethasone therapeutic use, Humans, Immunoelectrophoresis, Immunoglobulin G blood, Immunoglobulin G urine, Lenalidomide, Male, Middle Aged, Multiple Myeloma immunology, Multiple Myeloma therapy, Recurrence, Stem Cell Transplantation, Thalidomide analogs & derivatives, Thalidomide therapeutic use, Immunoglobulin kappa-Chains blood, Immunoglobulin kappa-Chains urine, Multiple Myeloma diagnosis
- Abstract
Multiple myeloma (MM) is characterized, in about 80% of cases, by the production of monoclonal intact immunoglobulin and more than 95% of them have elevated concentrations of involved (i.e. of the same class of intact immunoglobulin) free light chain (FLC). The introduction of novel therapeutic strategies has changed the natural history of the disease, leading to new manifestations of relapse. Light chain escape (LCE) is a pattern of relapse in which the FLC increase is not accompanied by a concomitant raise of the original monoclonal component (MC). Here we present a case of a 55-year-old man with an IgG kappa MM stage III diagnosed in September 2007. At presentation an IgG kappa MC and urine Bence Jones protein (BJP) kappa were present. Bone marrow biopsy (BMB) showed the presence of 80% monotypic kappa plasma cells (PCs). The patient received bortezomib, thalidomide, dexamethasone before undergoing a double autologous stem cell transplantation (ASCT) in October 2008 and April 2009. In May 2011 he relapsed showing the same pattern of presentation and treatment with lenalidomide and dexamethasone was started. ln May 2013 serum and urine immunofixation and FLC became negative. In September 2014, an increase of kappa FLC was observed, while serum and urine immunofixations remained negative until January 2015, when urine immunofixation became positive. Eventually, in February 2015, serum immunofixation revealed the presence of a free kappa MC. After a new BMB showing 80% of monotypic kappa PCs, a LCE relapse was diagnosed and the patient started the treatment with bendamustine, bortezomib and dexamethasone. In the present case, the increase of kappa FLC has indicated relapse 4 and 5 months earlier than urine and serum IFE, respectively. Our observation confirms that it is advisable to routinely perform FLC or BJP during follow up of MM patients undergoing ASCT and/or treatment with biological drugs to ensure that LCE is not missed.
- Published
- 2016
- Full Text
- View/download PDF
24. Diagnosis of ventilator-associated pneumonia: a pilot, exploratory analysis of a new score based on procalcitonin and chest echography.
- Author
-
Zagli G, Cozzolino M, Terreni A, Biagioli T, Caldini AL, and Peris A
- Subjects
- Aged, Analysis of Variance, Biomarkers blood, Calcitonin Gene-Related Peptide, Case-Control Studies, Critical Care methods, Critical Illness, Female, Humans, Intensive Care Units, Italy, Logistic Models, Male, Middle Aged, Pilot Projects, Pneumonia, Ventilator-Associated blood, Pneumonia, Ventilator-Associated diagnostic imaging, Predictive Value of Tests, Prognosis, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Survival Analysis, Ultrasonography, Doppler methods, Calcitonin blood, Hospital Mortality, Pneumonia, Ventilator-Associated diagnosis, Pneumonia, Ventilator-Associated mortality, Protein Precursors blood
- Abstract
Background: To facilitate the clinical diagnosis of ventilator-associated pneumonia (VAP) in the ICU, the Clinical Pulmonary Infection Score (CPIS) has been proposed but has shown a low diagnostic performance in subsequent studies. We propose a new score based on procalcitonin level and chest echography with the aim of improving VAP diagnosis: the Chest Echography and Procalcitonin Pulmonary Infection Score (CEPPIS)., Methods: This retrospective pilot study recruited patients admitted to the Intensive Care Unit of the Emergency Department, Careggi University Hospital (Florence, Italy), from January 2009 to December 2011. Patients were retrospectively divided into a microbiologically confirmed VAP group or a control group based on diagnosis of VAP and positive tracheal aspirate culture., Results: A total of 221 patients were included, with 113 in the microbiologically confirmed VAP group and 108 in the control group. A CEPPIS > 5 retrospectively fixed was significantly better in predicting VAP (OR, 23.78; sensitivity, 80.5%; specificity, 85.2%) than a CPIS > 6 (OR, 3.309; sensitivity, 39.8%; specificity, 83.3%). The receiver operating characteristic area under the curve analysis also showed a significantly higher diagnostic value for CEPPIS > 5 than CPIS > 6 (0.829 vs 0.616, respectively; P < .0001)., Conclusions: In this pilot, exploratory analysis, CEPPIS is effective in predicting VAP. Prospective validation is needed to confirm the potential value of this score to facilitate VAP diagnosis.
- Published
- 2014
- Full Text
- View/download PDF
25. A rare condition: IgE type monoclonal gammopathy of undetermined significance.
- Author
-
Caldini A, Balboni F, Parronchi P, Scoccianti S, Biagioli T, Terreni A, Morrocchi B, Brogi M, Berardi M, and Graziani M
- Subjects
- Aged, Humans, Male, Monoclonal Gammopathy of Undetermined Significance metabolism, Multiple Myeloma metabolism, Immunoglobulin E metabolism, Monoclonal Gammopathy of Undetermined Significance pathology, Multiple Myeloma pathology
- Published
- 2014
- Full Text
- View/download PDF
26. Is procalcitonin a reliable marker of sepsis in critically ill septic patients undergoing continuous veno-venous hemodiafiltration with "high cut-off" membranes (HCO-CVVHDF)?
- Author
-
Caldini A, Chelazzi C, Terreni A, Biagioli T, Giannoni C, Villa G, Messeri G, and De Gaudio AR
- Subjects
- Acute Kidney Injury complications, Biomarkers blood, C-Reactive Protein metabolism, Calcitonin Gene-Related Peptide, Critical Illness, Humans, Sepsis complications, Calcitonin blood, Hemofiltration methods, Membranes, Artificial, Protein Precursors blood, Sepsis blood, Sepsis therapy, Veins
- Published
- 2013
- Full Text
- View/download PDF
27. Carbon nanotube scaffolds instruct human dendritic cells: modulating immune responses by contacts at the nanoscale.
- Author
-
Aldinucci A, Turco A, Biagioli T, Toma FM, Bani D, Guasti D, Manuelli C, Rizzetto L, Cavalieri D, Massacesi L, Mello T, Scaini D, Bianco A, Ballerini L, Prato M, and Ballerini C
- Subjects
- Cell Adhesion immunology, Dendritic Cells cytology, Dendritic Cells immunology, Humans, Nerve Net chemistry, Nerve Net immunology, Neurons chemistry, Neurons immunology, Tissue Scaffolds chemistry, Dendritic Cells chemistry, Immunity, Innate, Nanotubes, Carbon chemistry, Tissue Engineering
- Abstract
Nanomaterials interact with cells and modify their function and biology. Manufacturing this ability can provide tissue-engineering scaffolds with nanostructures able to influence tissue growth and performance. Carbon nanotube compatibility with biomolecules motivated ongoing interest in the development of biosensors and devices including such materials. More recently, carbon nanotubes have been applied in several areas of nerve tissue engineering to study cell behavior or to instruct the growth and organization of neural networks. To gather further knowledge on the true potential of future constructs, in particular to assess their immune-modulatory action, we evaluate carbon nanotubes interactions with human dendritic cells (DCs). DCs are professional antigen-presenting cells and their behavior can predict immune responses triggered by adhesion-dependent signaling. Here, we incorporate DC cultures to carbon nanotubes and we show by phenotype, microscopy, and transcriptional analysis that in vitro differentiated and activated DCs show when interfaced to carbon nanotubes a lower immunogenic profile.
- Published
- 2013
- Full Text
- View/download PDF
28. PARP-1 inhibition prevents CNS migration of dendritic cells during EAE, suppressing the encephalitogenic response and relapse severity.
- Author
-
Cavone L, Aldinucci A, Ballerini C, Biagioli T, Moroni F, and Chiarugi A
- Subjects
- Analysis of Variance, Animals, Antigen Presentation drug effects, Autoimmunity drug effects, Cells, Cultured, Central Nervous System enzymology, Central Nervous System immunology, Central Nervous System pathology, Cytokines metabolism, Dendritic Cells enzymology, Dendritic Cells immunology, Dendritic Cells pathology, Encephalomyelitis, Autoimmune, Experimental enzymology, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental pathology, Female, Mice, Mice, Inbred C57BL, NF-kappa B metabolism, Ovalbumin immunology, Phenanthrenes pharmacology, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases metabolism, Recurrence, Severity of Illness Index, Th17 Cells drug effects, Th17 Cells enzymology, Th17 Cells immunology, Time Factors, Cell Movement drug effects, Central Nervous System drug effects, Dendritic Cells drug effects, Encephalomyelitis, Autoimmune, Experimental drug therapy, Enzyme Inhibitors pharmacology, Neuroprotective Agents pharmacology, Poly(ADP-ribose) Polymerase Inhibitors
- Abstract
Background: Pharmacological inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) are currently evaluated in clinical trials for various malignancies but, interestingly, also proved of remarkable efficacy in preclinical models of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE)., Objectives: The objectives of the study were to determine molecular mechanisms underlying suppression of the encephalitogenic response by these drugs; likewise, whether clinically-relevant post-treatment paradigms with PARP-1 inhibitors could prevent EAE relapses., Methods: Adopted both in vitro techniques (bone marrow-derived cultured DC) as well as in vivo models of chronic or relapsing-remitting (RR) EAE., Results: We report that two structurally unrelated PARP-1 inhibitors negatively regulated NFκB activation, as well as maturation, cytokine production and APC function of cultured mouse bone marrow-derived dendritic cells (DCs). PARP-1 inhibitors also reduced the number and APC function of DCs migrating in the draining lymph nodes of ovalbumin-immunized mice. In C57Bl mice with chronic EAE or SJL mice with RR EAE, pharmacological inhibition of PARP-1 reduced CNS DC migration and demyelination as well as neurological impairment to an extent similar to that achieved with the potent immunosuppressant cyclosporine A. Remarkably, PARP-1 inhibitors injected after the first phase of disease reduced relapse incidence and severity, as well as the spinal cord number of autoreactive Th17 cells. Under this clinically-relevant treatment paradigm, PARP inhibitors also suppressed epitope spreading of the encephalitogenic response., Conclusions: Overall, data underscore the potential relevance of PARP-1 inhibitors to MS therapy and suppression of autoimmunity.
- Published
- 2011
- Full Text
- View/download PDF
29. Inhibition of immune synapse by altered dendritic cell actin distribution: a new pathway of mesenchymal stem cell immune regulation.
- Author
-
Aldinucci A, Rizzetto L, Pieri L, Nosi D, Romagnoli P, Biagioli T, Mazzanti B, Saccardi R, Beltrame L, Massacesi L, Cavalieri D, and Ballerini C
- Subjects
- Actins ultrastructure, Cell Communication genetics, Cell Separation, Cells, Cultured, Coculture Techniques, Cytoskeleton immunology, Cytoskeleton metabolism, Cytoskeleton ultrastructure, Dendritic Cells metabolism, Dendritic Cells ultrastructure, Flow Cytometry, Gene Expression, Gene Expression Profiling, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Immunological Synapses ultrastructure, Lymphocyte Activation immunology, Mesenchymal Stem Cells ultrastructure, Microscopy, Confocal, Microscopy, Electron, Transmission, Microscopy, Immunoelectron, Actins metabolism, Cell Communication immunology, Dendritic Cells immunology, Immunological Synapses immunology, Mesenchymal Stem Cells immunology
- Abstract
Immune synapse formation between dendritic cells (DCs) and T cells is one of the key events in immune reaction. In immunogenic synapses, the presence of fully mature DCs is mandatory; consequently, the modulation of DC maturation may promote tolerance and represents a valuable therapeutic approach in autoimmune diseases. In the field of cell therapy, bone marrow mesenchymal stem cells (MSCs) have been extensively studied for their immunoregulatory properties, such as inhibiting DC immunogenicity during in vitro differentiation and ameliorating in vivo models of autoimmune diseases (e.g., experimental allergic encephalomyelitis). MSCs seem to play different roles with regard to DCs, depending on cell concentration, mechanism of stimulation, and accompanying immune cells. The aim of this work was to elucidate the immunogenic effects of MSC/DC interactions during DC activation (LPS stimulation or Ag loading). Human monocyte-derived DCs, bone marrow-derived MSCs, and circulating lymphocytes obtained from healthy donors, as well as the laboratory-generated influenza virus hemagglutinin-derived peptide, aa 306-318 peptide-specific T cell line were used for this study. We demonstrate that MSCs mediate inhibition of DC function only upon cell-cell contact. Despite no modification observed in cell phenotype or cytokine production, MSC-treated DCs were unable to form active immune synapses; they retained endocytic activity and podosome-like structures, typical of immature DCs. The transcriptional program induced by MSC-DC direct interaction supports at the molecular pathway level the phenotypical features observed, indicating the genes involved into contact-induced rearrangement of DC cytoskeleton.
- Published
- 2010
- Full Text
- View/download PDF
30. Modulating dendritic cells (DC) from immunogenic to tolerogenic responses: a novel mechanism of AZA/6-MP.
- Author
-
Aldinucci A, Biagioli T, Manuelli C, Repice AM, Massacesi L, and Ballerini C
- Subjects
- Adult, Cell Differentiation drug effects, Cell Differentiation immunology, Cells, Cultured, Dendritic Cells cytology, Dendritic Cells immunology, Female, Humans, Lymphocyte Culture Test, Mixed, Male, Middle Aged, Receptors, CCR7 biosynthesis, Receptors, CCR7 drug effects, Azathioprine pharmacology, Dendritic Cells drug effects, Immune Tolerance drug effects, Immunosuppressive Agents pharmacology, Multiple Sclerosis, Relapsing-Remitting immunology
- Abstract
Azathioprine (Aza), 6-Mercaptopurine (6-MP) and 6-Thioguanine (6-TG) are thiopurine drugs widely used as immunosuppressants/anti-inflammatory agents in organ transplantation and chemotherapy. Aza is well tolerated and effective in modifying the course of MS. Here we investigated the action of 6-MP on human dendritic cells (DCs). We described for the first time that 6-MP impairs in vitro differentiation of DCs, has an inhibitory effect during DC activation processes inducing a functionally less immunogenic phenotype. Moreover, 6-MP significantly reduces DC IL-23 production and CCR7 expression, at the same time induces IL-10 augmentation. All these findings add a novel action mechanism in Aza immune modulation., (Copyright 2009 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
31. Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution.
- Author
-
Bizzoco E, Lolli F, Repice AM, Hakiki B, Falcini M, Barilaro A, Taiuti R, Siracusa G, Amato MP, Biagioli T, Lori S, Moretti M, Vinattieri A, Nencini P, Massacesi L, and Matà S
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Animals, Child, Child, Preschool, Cross-Sectional Studies, Demyelinating Autoimmune Diseases, CNS epidemiology, Demyelinating Autoimmune Diseases, CNS physiopathology, Female, Humans, Italy epidemiology, Longitudinal Studies, Male, Middle Aged, Oligoclonal Bands blood, Oligoclonal Bands cerebrospinal fluid, Prevalence, Rats, Retrospective Studies, Severity of Illness Index, Statistics, Nonparametric, Young Adult, Neuromyelitis Optica epidemiology, Neuromyelitis Optica physiopathology, Phenotype
- Abstract
Neuromyelitis optica spectrum disorder (NMOsd) is a group of demyelinating disorders recently redefined and associated with NMO-IgG/anti-aquaporin 4 antibodies. Because NMOsd is of unknown prevalence worldwide, we conducted a retrospective, cross-sectional study of 850 patients with demyelinating disorders hospitalized in North East Tuscany from 1998 to 2006 to examine the prevalence of NMO and related disorders among unselected consecutive neurological patients with inflammatory CNS diseases and to evaluate the clinical phenotype spectrum of identified cases. Clinical data were updated after at least 2 years of follow-up. An immunofluorescence technique was used to detect NMO-IgG on rat brain tissue. Sera from other 828 neurological patients, 65 non-neurological patients and 50 healthy donors served as controls. The prevalence of NMOsd was 1.5%, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up. The final EDSS score ranged from 1 to 10, mainly depending on brainstem involvement occurrence. Our findings confirm a low prevalence of NMO and related disorders among demyelinating inflammatory diseases in a Caucasian population. Moreover, this study demonstrates an unexpectedly high prevalence of limited and atypical variants of this disease, not previously documented.
- Published
- 2009
- Full Text
- View/download PDF
32. Differences in mesenchymal stem cell cytokine profiles between MS patients and healthy donors: implication for assessment of disease activity and treatment.
- Author
-
Mazzanti B, Aldinucci A, Biagioli T, Barilaro A, Urbani S, Dal Pozzo S, Amato MP, Siracusa G, Crescioli C, Manuelli C, Bosi A, Saccardi R, Massacesi L, and Ballerini C
- Subjects
- Adult, Cell Differentiation immunology, Cell Proliferation, Female, Flow Cytometry, Humans, Male, Middle Aged, Phenotype, Toll-Like Receptors biosynthesis, Cytokines metabolism, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells immunology, Mesenchymal Stem Cells metabolism, Multiple Sclerosis immunology, Receptors, Cytokine biosynthesis
- Abstract
MSCs have been proposed as possible treatment in MS: In this study MSCs obtained from 10 MS patients and 6 healthy donors (HD) were compared in terms of phenotypical and functional characteristics. We show that MSCs isolated from MS and HD differ significantly for IP10 production. Therefore, although MSCs isolated from MS patients exhibit the same properties of HD MSCs in terms of proliferation, phenotype, in vitro differentiation, TLR expression, immunosuppressive ability, inhibition of DC differentiation and activation, the use of autologous MSCs in cell therapy of autoimmune diseases should be submitted to attentive evaluation and treatment.
- Published
- 2008
- Full Text
- View/download PDF
33. Combined treatment with atorvastatin and minocycline suppresses severity of EAE.
- Author
-
Luccarini I, Ballerini C, Biagioli T, Biamonte F, Bellucci A, Rosi MC, Grossi C, Massacesi L, and Casamenti F
- Subjects
- Animals, Atorvastatin, Body Weight drug effects, Cell Proliferation drug effects, Cytokines metabolism, Drug Therapy, Combination, Enzyme-Linked Immunosorbent Assay, Female, Glial Fibrillary Acidic Protein metabolism, Glycoproteins pharmacology, Mice, Mice, Inbred C57BL, Myelin-Oligodendrocyte Glycoprotein, Neurologic Examination, Peptide Fragments pharmacology, Stereotaxic Techniques, T-Lymphocytes drug effects, Time Factors, Anti-Bacterial Agents therapeutic use, Encephalomyelitis, Autoimmune, Experimental drug therapy, Heptanoic Acids therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Minocycline therapeutic use, Multiple Sclerosis drug therapy, Pyrroles therapeutic use
- Abstract
Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). An approach to improve MS treatment is to identify a rational combination of new medications or existing therapies that impact different aspects of the disease process. Statins are effective in the treatment of MS animal models and are promising candidates for future treatment. Minocycline ameliorates clinical severity of experimental autoimmune encephalomyelitis (EAE) and exhibits several anti-inflammatory and neuroprotective activities. In this study, we tested whether the combination of these two drugs could produce beneficial effects in EAE mice immunized with myelin oligodendrocyte protein (MOG). Our findings show that combined treatment, compared to using the medications alone, resulted in a significant reduction in disease severity, in both the acute and chronic phases of the disease, along with attenuation of inflammation, demyelination and axonal loss. Stereological analysis revealed that the combined treatment significantly guarded against neuroinflammation and neurodegeneration. Moreover, a significant suppression of anti-MOG antibody production in animals treated with the two medications was found. In conclusion, our findings prove that this combination of drugs is neuroprotective and suppresses the severity of EAE. Furthermore, this pharmacological approach appears to be promising as a future therapeutic strategy to control MS.
- Published
- 2008
- Full Text
- View/download PDF
34. Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction.
- Author
-
Liotta F, Frosali F, Querci V, Mantei A, Filì L, Maggi L, Mazzinghi B, Angeli R, Ronconi E, Santarlasci V, Biagioli T, Lasagni L, Ballerini C, Parronchi P, Scheffold A, Cosmi L, Maggi E, Romagnani S, and Annunziato F
- Subjects
- CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Calcium-Binding Proteins physiology, Cells, Cultured, Dendritic Cells cytology, Dendritic Cells metabolism, GATA3 Transcription Factor biosynthesis, GATA3 Transcription Factor genetics, Humans, Immunophenotyping, Intercellular Signaling Peptides and Proteins physiology, Jagged-1 Protein, Membrane Proteins physiology, Myeloid Progenitor Cells cytology, Myeloid Progenitor Cells metabolism, Receptors, Notch physiology, Serrate-Jagged Proteins, T-Box Domain Proteins biosynthesis, T-Box Domain Proteins genetics, Th2 Cells cytology, Up-Regulation genetics, Up-Regulation immunology, Calcium-Binding Proteins metabolism, Cell Communication immunology, Cell Differentiation immunology, Dendritic Cells immunology, Intercellular Signaling Peptides and Proteins metabolism, Membrane Proteins metabolism, Myeloid Progenitor Cells immunology, Receptors, Notch metabolism, Th2 Cells immunology, Th2 Cells metabolism
- Abstract
Background: The mechanisms by which human dendritic cells (DCs) activate a TH1-polarizing or TH2-polarizing program are still partially unclear., Objective: Study of the mechanisms responsible for the TH1/TH2-polarizing activity of human circulating myeloid DCs before and after ligation of their Toll-like receptors (TLRs)., Methods: IL-4 and IFN-gamma production by CD4+ T cells was assessed in cocultures with myeloid DCs before or after TLR triggering. Expression of Jagged-1 and Delta-4 Notch ligands and of GATA-3 and T-box expressed in T cells transcription factors was evaluated by real-time quantitative PCR. Signal transducer and activator of transcription 4 and 6 phosphorylation was assessed by flow cytometry. Knockdown of Jagged-1 or Delta-4 was performed by transfection of DCs with appropriate silencing mRNAs., Results: Myeloid immature DCs constitutively expressed Jagged-1, which induces in CD4+ T cells a TH2 polarization, as shown by Jagged-1 gene silencing. The TH2 polarization associated with high GATA-3/T-box expressed in T cells ratio and was at least partially dependent on the early induction of IL-4. Maturation of DCs by TLR ligation resulted in the reduction of Jagged-1 and upregulation of Delta-4, which was at least in part responsible for the polarization of CD4+ T cells to the TH1 phenotype., Conclusion: CD4+ T-cell responses are usually characterized by a prevalent TH2 phenotype unless TLRs are triggered on DCs by microbial components.
- Published
- 2008
- Full Text
- View/download PDF
35. HCV patients, psychopathology and tryptophan metabolism: analysis of the effects of pegylated interferon plus ribavirin treatment.
- Author
-
Zignego AL, Cozzi A, Carpenedo R, Giannini C, Rosselli M, Biagioli T, Aldinucci A, Laffi G, and Moroni F
- Subjects
- Drug Therapy, Combination, Female, Hepatitis C, Chronic drug therapy, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Interferon alpha-2, Kynurenine blood, Macrophages enzymology, Male, Middle Aged, Recombinant Proteins, Antiviral Agents administration & dosage, Hepatitis C, Chronic complications, Hepatitis C, Chronic metabolism, Interferon-alpha administration & dosage, Polyethylene Glycols administration & dosage, Ribavirin administration & dosage, Tryptophan blood
- Abstract
Aims: Depression and other psychiatric disorders are frequent in HCV-infected patients, especially during interferon treatment. The molecular mechanism(s) underlying this finding is still unknown but it has been suggested that HCV and/or interferon administration may increase indoleamine 2,3-dioxygenase (IDO) activity, and reduce plasma tryptophan (TRP) levels and brain serotonin synthesis thus leading to psychopathological disorders., Methods: We studied 89 subjects: (a) 39 patients with chronic hepatitis C virus (HCV) infection and mild liver damage; (b) 39 healthy controls; and (c) 10 patients with chronic hepatitis B virus (HBV) infection. 15 of the patients with HCV infection were re-evaluated after antiviral treatment with pegylated interferon alpha-2a plus ribavirin leading to viral eradication. We measured serum TRP and kynurenine levels and IDO activity in macrophages. Furthermore, each patient had an accurate psychopathological evaluation., Results: HCV-infected patients had lower (-28%) serum TRP and kynurenine levels than healthy volunteers or HBV-infected patients with comparable liver damage. Depression and anxiety symptoms were particularly common in HCV patients. After viral clearance, macrophage IDO activity, plasma TRP and kynurenine levels returned toward normal values and psychopathology improved., Conclusion: Our study shows that HCV patients have reduced serum TRP levels and confirms that they frequently suffer from anxiety and depression-related symptoms. The reduced IDO activity found in the macrophages of these patients suggests that HCV infection may hamper macrophage functions. After successful antiviral treatment, in spite of the expected increase of IDO activity in macrophages, we noticed that TRP and kynurenine plasma levels returned toward physiological levels and psychopathology decreased significantly.
- Published
- 2007
- Full Text
- View/download PDF
36. A key role for poly(ADP-ribose) polymerase-1 activity during human dendritic cell maturation.
- Author
-
Aldinucci A, Gerlini G, Fossati S, Cipriani G, Ballerini C, Biagioli T, Pimpinelli N, Borgognoni L, Massacesi L, Moroni F, and Chiarugi A
- Subjects
- Cell Differentiation drug effects, Cells, Cultured, DNA-Binding Proteins antagonists & inhibitors, DNA-Binding Proteins metabolism, Dendritic Cells drug effects, Down-Regulation drug effects, Down-Regulation immunology, Enzyme Activation drug effects, Enzyme Inhibitors pharmacology, Humans, Immunophenotyping, Interleukin-10 antagonists & inhibitors, Interleukin-10 biosynthesis, Interleukin-12 antagonists & inhibitors, Interleukin-12 biosynthesis, Lymphocyte Activation drug effects, Monocytes cytology, Monocytes enzymology, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases biosynthesis, Transcription Factor AP-1 antagonists & inhibitors, Transcription Factor AP-1 metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Cell Differentiation immunology, Dendritic Cells cytology, Dendritic Cells enzymology, Poly(ADP-ribose) Polymerases metabolism
- Abstract
Poly(ADP-ribose) (PAR) polymerase (PARP)-1 is a nuclear enzyme regulating protein that functions by targeting PAR chains. Besides its classic role in DNA repair, PARP-1 is emerging as a key transcriptional regulator in different cell types including the immune ones. In this study, we investigated the role of PARP-1 in human dendritic cell (DC) function. We report that both PARP-1 mRNA and protein levels significantly increased during in vitro DC differentiation from monocytes. Of note, inhibitors of PARP-1 such as phenanthridinone and thieno[2,3-c]isoquinolin-5-one reduced expression of CD86 and CD83 in a concentration-dependent manner, having no effects on expression of CD80 and HLA-DR in mature DCs. In the same cultures, PARP-1 inhibitors also reduced production of IL-12 and IL-10. Addition of exogenous IL-12 to the culture medium partially restored CD86 expression in DCs exposed to PARP-1 inhibitors. In line with the role of PAR formation in NF-kappaB-dependent transactivation, we also report that phenanthridinone and thieno[2,3-c]isoquinolin-5-one impaired NF-kappaB and AP-1 subunit DNA binding activity in cellular extract of activated DCs. Finally, we show that PARP-1 inhibitors reduced the T cell allostimulatory activity of mature DCs, and that this reduction was prevented when DCs matured in the presence of PARP-1 inhibitors plus IL-12. Of note, nonproliferating T cells exposed to PARP-1 inhibitor-challenged DCs could undergo efficient proliferation when exposed to a subsequent activation stimulus such as anti-CD3 plus anti-CD-28. Together, data provide evidence for a key role of PARP-1 and poly ADP-ribosylation in DC immunocompetence and underscore the relevance of PARP-1 inhibitors to treatment of immune disorders.
- Published
- 2007
- Full Text
- View/download PDF
37. Effects of pixantrone on immune-cell function in the course of acute rat experimental allergic encephalomyelitis.
- Author
-
Mazzanti B, Biagioli T, Aldinucci A, Cavaletti G, Cavalletti E, Oggioni N, Frigo M, Rota S, Tagliabue E, Ballerini C, Massacesi L, Riccio P, and Lolli F
- Subjects
- Analysis of Variance, Animals, Antibodies blood, Antigens, CD immunology, Antigens, CD metabolism, Apoptosis drug effects, B-Lymphocytes physiology, Cell Proliferation drug effects, Cytokines metabolism, Cytokinesis, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay methods, Female, Flow Cytometry methods, Myelin Basic Protein administration & dosage, Myelin Basic Protein immunology, Rats, Rats, Inbred Lew, T-Lymphocytes drug effects, Time Factors, B-Lymphocytes drug effects, Encephalomyelitis, Autoimmune, Experimental drug therapy, Immunosuppressive Agents therapeutic use, Isoquinolines therapeutic use
- Abstract
Pixantrone is an immunesuppressor similar to mitoxantrone but with lower cardiotoxicity. We evaluated the effect of pixantrone on B cells and lymphomononuclear cells in the course of acute EAE. Pixantrone reduced the number of B cells and suppressed myelin basic protein (MBP) specific IgG production. In vitro, pixantrone induced apoptosis of rat B lymphocytes in a way similar to mitoxantrone. In addition, pixantrone inhibited antigen specific and mitogen induced lymphomononuclear cell proliferation, as well as IFN-gamma production, during EAE. These findings suggest a similar mechanism of action for pixantrone and mitoxantrone on the effector function of lymphomonocyte B and T cells.
- Published
- 2005
- Full Text
- View/download PDF
38. Design and synthesis of a novel potent myelin basic protein epitope 87-99 cyclic analogue: enhanced stability and biological properties of mimics render them a potentially new class of immunomodulators.
- Author
-
Matsoukas J, Apostolopoulos V, Kalbacher H, Papini AM, Tselios T, Chatzantoni K, Biagioli T, Lolli F, Deraos S, Papathanassopoulos P, Troganis A, Mantzourani E, Mavromoustakos T, and Mouzaki A
- Subjects
- Adjuvants, Immunologic chemistry, Adjuvants, Immunologic pharmacology, Animals, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes drug effects, Cell Line, Cell Proliferation drug effects, Cyclization, Cytokines metabolism, Drug Stability, Encephalomyelitis, Autoimmune, Experimental chemically induced, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental immunology, Epitopes, HLA-DR4 Antigen metabolism, Humans, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Lysosomes enzymology, Models, Molecular, Molecular Mimicry, Multiple Sclerosis blood, Multiple Sclerosis immunology, Mutation, Myelin Basic Protein pharmacology, Peptides, Cyclic chemistry, Peptides, Cyclic pharmacology, Protein Binding, Rats, Rats, Inbred Lew, Th1 Cells drug effects, Th1 Cells metabolism, Th2 Cells drug effects, Th2 Cells metabolism, Adjuvants, Immunologic chemical synthesis, Myelin Basic Protein chemical synthesis, Myelin Basic Protein chemistry, Peptide Fragments chemistry, Peptides, Cyclic chemical synthesis
- Abstract
A cyclic analogue, [cyclo(87-99)MBP(87)(-)(99)], of the human immunodominant MBP(87)(-)(99) epitope, was designed based on ROESY/NMR distance information and modeling data for linear epitope 87-99, taking into account T-cell (Phe(89), Lys(91), Pro(96)) and HLA (His(88), Phe(90), Ile(93)) contact side-chain information. The cyclic analogue was found to induce experimental allergic encephalomyelitis (EAE), to bind HLA-DR4, and to increase CD4 T-cell line proliferation, like that of the conformationally related linear MBP(87)(-)(99) epitope peptide. The mutant cyclic peptides, the cyclo(91-99)[Ala(96)]MBP(87)(-)(99) and the cyclo(87-99)[Arg(91)Ala(96)]MBP(87)(-)(99), reported previously for suppressing, to a varying degree, autoimmune encephalomyelitis in a rat animal model, were found in this study to possess the following immunomodulatory properties: (i) they suppressed the proliferation of a CD4 T-cell line raised from a multiple sclerosis patient, (ii) they scored the best in vitro TH2/TH1 cytokine ratio in peripheral blood mononuclear cell cultures derived from 13 multiple sclerosis patients, inducing IL-10 selectively, and (iii) they bound to HLA-DR4, first to be reported for cyclic MBP peptides. In addition, cyclic peptides were found to be more stable to lysosomal enzymes and Cathepsin B, D, and H, compared to their linear counterparts. Taken together, these data render cyclic mimics as putative drugs for treating multiple sclerosis and potentially other Th1-mediated autoimmune diseases.
- Published
- 2005
- Full Text
- View/download PDF
39. A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population.
- Author
-
Liguori M, Sawcer S, Setakis E, Compston A, Giordano M, D'Alfonso S, Mellai M, Malferrari G, Trojano M, Livrea P, De Robertis F, Massacesi L, Repice A, Ballerini C, Biagioli T, Bomprezzi R, Cannoni S, Ristori G, Salvetti M, Grimaldi LM, Biunno I, Comi G, Leone M, Ferro I, Naldi P, Milanese C, Gellera C, Loredana LM, Savettieri G, Salemi G, Aridon P, Caputo D, Rosa Guerini F, Ferrante P, and Momigliano-Richiardi P
- Subjects
- Alleles, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, International Cooperation, Italy epidemiology, Male, Microsatellite Repeats, Multiple Sclerosis epidemiology, Racial Groups genetics, Genetic Testing methods, Genetic Testing statistics & numerical data, Genome, Human, Linkage Disequilibrium genetics, Multiple Sclerosis genetics
- Abstract
We have systematically screened the genome for evidence of linkage disequilibrium (LD) with multiple sclerosis (MS) by typing 6000 microsatellite markers in case-control and family based (AFBAC) cohorts from the Italian population. DNA pooling was used to reduce the genotyping effort involved. Four DNA pools were considered: cases (224 Italian MS patients), controls (231 healthy Italians), index (185 index cases from trio families) and parents (the 370 parents of the patient included in the Index pool), respectively. After refining analysis of the most promising 14 markers to emerge from this screening process, only marker D2S367 retained evidence for association.
- Published
- 2003
- Full Text
- View/download PDF
40. Protein tyrosine phosphatase receptor-type C exon 4 gene mutation distribution in an Italian multiple sclerosis population.
- Author
-
Ballerini C, Rosati E, Salvetti M, Ristori G, Cannoni S, Biagioli T, Massacesi L, Sorbi S, and Vergelli M
- Subjects
- Base Sequence genetics, Case-Control Studies, Gene Frequency, Genetic Predisposition to Disease, Humans, Italy, Leukocyte Common Antigens genetics, Reference Values, Exons, Multiple Sclerosis genetics, Mutation physiology
- Abstract
In this study, we investigate the role of the C-->G mutation in position 77 of exon 4 of the protein tyrosine phosphatase receptor-type C (PTPRC) gene, coding for the CD45 molecule, for the development of multiple sclerosis (MS) in an Italian continental population. The PTPRC mutated genotype has been recently described as associated with MS in three different case-control studies carried out in German MS patients, whereas similar studies performed in the US and Swedish populations failed to demonstrate such an association. The C-->G transition in position 77 was found in a small number of Italian MS patients and in none of the matched group of healthy controls (Fisher exact test, P value=0.02). This finding suggests a role, in at least a group of patients, for the PTPRC mutation in genetic susceptibility to MS.
- Published
- 2002
- Full Text
- View/download PDF
41. IL-7-enhanced T-cell response to myelin proteins in multiple sclerosis.
- Author
-
Traggiai E, Biagioli T, Rosati E, Ballerini C, Mazzanti B, Ben Nun A, Massacesi L, and Vergelli M
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, In Vitro Techniques, Male, Middle Aged, Myelin Basic Protein immunology, Myelin Proteins, Myelin-Associated Glycoprotein immunology, Myelin-Oligodendrocyte Glycoprotein, T-Lymphocytes drug effects, Interleukin-7 pharmacology, Multiple Sclerosis, Chronic Progressive immunology, Multiple Sclerosis, Relapsing-Remitting immunology, Myelin Basic Protein pharmacology, Myelin-Associated Glycoprotein pharmacology, T-Lymphocytes immunology
- Abstract
In this study, we investigated the in vitro proliferative response of peripheral blood T lymphocytes from MS patients and controls to MBP and MOG either in the absence or in the presence of the conditioning factor IL-7. In the absence of IL-7, T-cell reactivity to MOG and MBP was similar in MS patients and controls even if an increased MBP response was found in a subgroup of patients with active disease. In the presence of IL-7, increased T-cell reactivity to MBP was observed in MS patients suggesting that their MBP-specific T cells are in a different functional state.
- Published
- 2001
- Full Text
- View/download PDF
42. Short-term evolution of autoreactive T cell repertoire in multiple sclerosis.
- Author
-
Vergelli M, Mazzanti B, Traggiai E, Biagioli T, Ballerini C, Parigi A, Konse A, Pellicanò G, and Massacesi L
- Subjects
- Adult, Antibody Specificity drug effects, Antibody Specificity immunology, Autoantigens pharmacology, Cell Division drug effects, Cell Division immunology, Cells, Cultured drug effects, Cells, Cultured immunology, Cells, Cultured metabolism, Central Nervous System metabolism, Central Nervous System pathology, Cytokines metabolism, Disease Progression, Epitopes, T-Lymphocyte immunology, Female, Humans, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-4 immunology, Interleukin-4 metabolism, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis metabolism, Myelin Basic Protein pharmacology, Peptides immunology, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Time Factors, Autoantigens immunology, Central Nervous System immunology, Cytokines immunology, Multiple Sclerosis immunology, Multiple Sclerosis pathology, Myelin Basic Protein immunology, T-Lymphocytes immunology
- Abstract
T cells reactive to self-antigens are present in the peripheral blood of patients with autoimmune diseases as well as in healthy subjects. Although T cell-response to the self-myelin antigen myelin basic protein (MBP) has been widely investigated in multiple sclerosis (MS) patients, very little is known about the evolution over time of this response and its correlation with the disease activity. In recent years magnetic resonance imaging (MRI) techniques have provided new tools for following the inflammatory activity in the central nervous system (CNS) of MS patients. In the present study the T cell response to MBP was longitudinally investigated in terms of frequency, epitope specificity, and cytokine production profile in four patients with relapsing-remitting MS enrolled in a gadolinium-enhanced MRI serial study. In spite of different profiles of inflammatory activity within the CNS, all the patients examined showed major changes in their reactivity to MBP during the follow-up period in terms of both frequency and epitope specificity. Episodic expansions of MBP-specific T cell populations were observed in each patient, and overall they did not correlate with disease activity. In these patients the expansions: 1) occurred in the context of a steady level of disease activity, 2) correlated with a burst of CNS inflammation, 3) followed the appearance of a new active lesion, and 4) were observed even in the absence of detectable signs of CNS inflammation during the entire follow-up period. These results suggest that the evolution over time of the T cell response to a self-antigen such as MBP is more complex than previously expected. The short-term repertoire dynamics of autoreactive T cells in MS underscore the importance of longitudinal studies for evaluating autoreactivity to myelin antigens and probably to any self-antigen in other autoimmune diseases., (Copyright 2001 Wiley-Liss, Inc.)
- Published
- 2001
- Full Text
- View/download PDF
43. Palmitoyl derivatives of GpMBP epitopes: T-cell response and peptidases susceptibility.
- Author
-
Papini AM, Mazzanti B, Nardi E, Traggiai E, Ballerini C, Biagioli T, Kalbacher H, Beck H, Deeg M, Chelli M, Ginanneschi M, Massacesi L, and Vergelli M
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, Cathepsin D chemistry, Cathepsin L, Cathepsins chemistry, Cell Division, Cysteine Endopeptidases, Epitopes, Female, In Vitro Techniques, Lipoproteins chemistry, Lipoproteins pharmacology, Lysosomes enzymology, Rats, Rats, Inbred Lew, Structure-Activity Relationship, CD4-Positive T-Lymphocytes drug effects, Lipoproteins chemical synthesis, Myelin Basic Protein immunology, Palmitic Acid chemistry, Peptide Fragments immunology, Peptide Hydrolases chemistry
- Abstract
We report for the first time the immunoadjuvant effects of lipoconjugation of peptide antigens in an in vitro system by using CD4+ T-cells. The lipopeptides obtained by conjugating a palmitoyl moiety at the N(alpha)-terminal of Gln(74) or at the epsilon-NH(2) of Lys(75) of GpMBP(74-85) induced increased T-cell responsiveness compared to the native nonlipidated peptide. On the other hand, lipoderivatives of GpMBP(82-98) did not increase the T-cell response, demonstrating that the superagonist inducing effect of lipoconjugation is epitope-specific. Digestion of the two native peptides with cathepsin D and L, both implicated in antigen processing, and with a complete lysosomal fraction of a EBV-transformed B cell line shows that GpMBP(74-85) is resistant to cellular proteases, while GpMBP(82-98) is easily digested by these enzymes. These results suggest that the first prerequisite for increasing the T-cell response by lipoconjugation is the stability of the native peptide to peptidases, providing an important insight into the understanding of the immunoadjuvant effect of lipoderivative antigens.
- Published
- 2001
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.