Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset
| Autor: | Paolo Gallo, Erica Stropparo, Giustina De Silvestro, Marco Puthenparampil, Mario Plebani, Antonio Zito, Silvia Miante, Lisa Federle, Giorgia Pantano |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male oligoclonal IgG synthesis Intrathecal T-Lymphocytes Regulatory Clinical onset Subarachnoid Space Immunoglobulin G Multiple sclerosis 03 medical and health sciences Multiple Sclerosis Relapsing-Remitting 0302 clinical medicine Text mining Humans Medicine 030212 general & internal medicine biology business.industry T-Lymphocytes Helper-Inducer Middle Aged medicine.disease Peripheral medicine.anatomical_structure follicular T-cell subsets Neurology Immunology biology.protein Female Lymph Nodes Neurology (clinical) Subarachnoid space business 030217 neurology & neurosurgery |
| Zdroj: | Multiple Sclerosis Journal. 25:918-926 |
| ISSN: | 1477-0970 1352-4585 |
| DOI: | 10.1177/1352458518779951 |
| Popis: | Background:Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell.Objective:To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients.Methods:Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25–CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127dim), conventional T-Helper (TH, CD3+CD4+CXCR5–CD25–CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5–CD25+CD127dim) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF.Results:Compared to HC, RRMS had lower TFR percentage ( p < 0.01) and higher TFH/TFR ratio ( p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative ( r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05).Conclusion:In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS. |
| Databáze: | OpenAIRE |
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