Gasperi, Christiane and Andlauer, Till F. M. and Keating, Ana and Knier, Benjamin and Klein, Ana and Pernpeintner, Verena and Lichtner, Peter and Gold, Ralf and Zipp, Frauke and Bergh, Florian Then and Stangel, Martin and Tumani, Hayrettin and Wildemann, Brigitte and Wiendl, Heinz and Bayas, Antonios and Kuempfel, Tania and Zettl, Uwe K. and Linker, Ralf A. and Ziemann, Ulf and Knop, Matthias and Warnke, Clemens and Friese, Manuel A. and Paul, Friedemann and Tackenberg, Bjoern and Berthele, Achim and Hemmer, Bernhard (2020) Genetic determinants of the humoral immune response in MS. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION, 7 (5): e827. ISSN 2332-7812,
Full text not available from this repository. (Request a copy)Abstract
Objective In 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). Methods Using 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. Results The minor alleles of variants on chromosome 14 were associated with higher intrathecal immunoglobulin G levels (beta = 0.58 [0.47 to 0.68], lowest adjusted p = 2.32 x 10(-23)), and lower intrathecal immunoglobulin M (beta = -0.56 [-0.67 to -0.46], p = 2.06 x 10(-24)) and A (beta = -0.42 [-0.54 to -0.31], p = 7.48 x 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 x 10(-7)) and HLA-B*44:02 with lower (beta = -0.35 [-0.54 to -0.17], p = 1.38 x 10(-2)) immunoglobulin G levels. Of interest, different HLA alleles were associated with lower intrathecal immunoglobulin M (HLA-C*02:02, beta = -0.45 [-0.61 to -0.28], p = 1.01 x 10(-5)) and higher immunoglobulin A levels (HLA-DQA1*01:03-DQB1*06:03-DRB1*13:01 haplotype, beta = 0.40 [0.21 to 0.60], p = 4.46 x 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. Conclusion Although 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIAGNOSTIC-CRITERIA; MULTIPLE-SCLEROSIS; IGG; GUIDELINES; ALLOTYPES; VARIANTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2021 11:45 |
| Last Modified: | 12 Mar 2021 11:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43915 |
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