Genetic determinants of the humoral immune response in MS
| Autor: | Benjamin Knier, Till F. M. Andlauer, Clemens Warnke, Antonios Bayas, Manuel A. Friese, Tania Kümpfel, Ana Keating, Verena Pernpeintner, Björn Tackenberg, Hayrettin Tumani, Heinz Wiendl, Florian Then Bergh, Martin Stangel, Uwe K. Zettl, Ralf Gold, M. Knop, Peter Lichtner, Achim Berthele, Frauke Zipp, Brigitte Wildemann, Friedemann Paul, Bernhard Hemmer, Ralf A. Linker, Ulf Ziemann, Christiane Gasperi, Ana Klein |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunoglobulin A Adult Male Multiple Sclerosis Human leukocyte antigen Major histocompatibility complex Immunoglobulin G Article Cohort Studies 03 medical and health sciences 0302 clinical medicine Medicine Humans ddc:610 Chromosomes Human Pair 14 biology business.industry Haplotype Histocompatibility Antigens Class I Histocompatibility Antigens Class II Middle Aged Molecular biology ddc 3. Good health Immunity Humoral 030104 developmental biology Neurology Immunoglobulin M biology.protein Immunoglobulin heavy chain Female Neurology (clinical) Antibody Function and Dysfunction of the Nervous System business 030217 neurology & neurosurgery |
| Zdroj: | Neurology® Neuroimmunology & Neuroinflammation Neurol. Neuroimmunol. Neuroinflammation 7:e827 (2020) Neurology-Neuroimmunology Neuroinflammation |
| ISSN: | 2332-7812 |
| Popis: | ObjectiveIn this observational study, we investigated the impact of genetic factors at the immunoglobulin heavy chain constant locus on chromosome 14 and the major histocompatibility complex region on intrathecal immunoglobulin G, A, and M levels as well as on B cells and plasmablasts in the CSF and blood of patients with multiple sclerosis (MS).MethodsUsing regression analyses, we tested genetic variants on chromosome 14 and imputed human leukocyte antigen (HLA) alleles for associations with intrathecal immunoglobulins in 1,279 patients with MS or clinically isolated syndrome and with blood and CSF B cells and plasmablasts in 301 and 348 patients, respectively.ResultsThe minor alleles of variants on chromosome 14 were associated with higher intrathecal immunoglobulin G levels (β = 0.58 [0.47 to 0.68], lowest adjusted p = 2.32 × 10−23), and lower intrathecal immunoglobulin M (β = −0.56 [−0.67 to −0.46], p = 2.06 × 10−24) and A (β = −0.42 [−0.54 to −0.31], p = 7.48 × 10−11) levels. Alleles from the HLA-B*07:02-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype were associated with higher (lowest p = 2.14 × 10−7) and HLA-B*44:02 with lower (β = −0.35 [−0.54 to −0.17], p = 1.38 × 10−2) immunoglobulin G levels. Of interest, different HLA alleles were associated with lower intrathecal immunoglobulin M (HLA-C*02:02, β = −0.45 [−0.61 to −0.28], p = 1.01 × 10−5) and higher immunoglobulin A levels (HLA-DQA1*01:03-DQB1*06:03-DRB1*13:01 haplotype, β = 0.40 [0.21 to 0.60], p = 4.46 × 10−3). The impact of HLA alleles on intrathecal immunoglobulin G and M levels could mostly be explained by associations with CSF B cells and plasmablasts.ConclusionAlthough some HLA alleles seem to primarily drive the extent of humoral immune responses in the CNS by increasing CSF B cells and plasmablasts, genetic variants at the immunoglobulin heavy chain constant locus might regulate intrathecal immunoglobulins levels via different mechanisms. |
| Databáze: | OpenAIRE |
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