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. 2025 Sep;55(9):e70049.
doi: 10.1002/eji.70049.

Perturbances in Both Circulating B and CD4+ T Cells Discriminate Multiple Sclerosis from Other Central Nervous System Autoimmune Diseases

Laurens Bogers  1 , Jasper Rip  1 , Suzanne C Franken  2 , Kirsten L Kuiper  1 , Ana M Marques  1 , Annet F Wierenga-Wolf  1 , Marie-José Melief  1 , Cato E A Corsten  3 , Romy A M Klein Kranenbarg  3   4 , Janet de Beukelaar  4 , Ide Smets  3 , Beatrijs H Wokke  3 , Maarten J Titulaer  2 , Joost Smolders  1   3   5 , Marvin M van Luijn  1
Affiliations

Perturbances in Both Circulating B and CD4+ T Cells Discriminate Multiple Sclerosis from Other Central Nervous System Autoimmune Diseases

Laurens Bogers et al. Eur J Immunol. 2025 Sep.

Abstract

Using spectral flow cytometry, we analyzed circulating lymphocyte subsets in treatment-naive individuals with multiple sclerosis (MS) and other central nervous system autoimmune diseases (CNS AIDs). Elevated B-cell and CD4+ T-cell frequencies were a disease-specific feature of MS, while reduced T-bet+ and CXCR3+ B-cell levels were associated with progressive disease.

Keywords: MOGAD; anti‐AQP4 NMOSD; autoimmune encephalitis; disease progression; disease specificity.

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Conflict of interest statement

I.S. has received speaker fees from Biogen, Merck, and Sanofi. M.J.T. has filed a patent, on behalf of the Erasmus MC, for methods for typing neurological disorders and cancer, as well as devices for use therein, and has received research funding from EpilepsieNL (NEF 14‐19 & 19‐08), Dioraphte (2001 0403), ZonMw (Memorabel fellowship, VIMP scheme and Open Competition [ACT‐MD]), ItsME, Erasmus MC Foundation, and Erasmus Trustfonds. M.J.T. has served on the scientific advisory board of Horizon Therapeutics/AmGen, ArgenX, and Arialys; for consultation at Guidepoint Global LLC, and at UCB. M.J.T. is co‐PI of the EXTINGUISH trial. M.J.T. has received unrestricted research grants from Euroimmun AG and CSL Behring. M.J.T. has filed a copyright on behalf of ErasmusMC for the PROSE (Patient‐Reported Outcome Scale in Encephalitis). J.S. reports grants for scientific research from Biogen, Hansa Biopharma, Roche, and Siemens Healthineers, and has received speaker and/or consultancy fees from Biogen, Merck, Novartis, Roche, and Sanofi. M.M.v.L. has received research support from EMD Serono, Merck, Novartis, GSK, and Idorsia Pharmaceutical Ltd. The remaining authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Increased B‐ and CD4+ T‐cell frequencies in blood of people with MS. (A) Thawed blood samples from healthy controls (young/old; n = 12) and treatment‐naive individuals with MS (relapsing/progressive; n = 12), AE (anti‐LGI1/‐IgLON5/‐GAD65; n = 10) or RDD (anti‐AQP4 NMOSD/MOGAD; n = 6) were analyzed using ex vivo spectral flow cytometry. (B) Gating strategy of B‐, T‐, and NK‐cell subsets. (C) B‐, T‐, and NK‐cell frequencies within viable lymphocytes. (D) CD4+ and CD8+ frequencies within total T cells. (E) CD4+/CD8+ T‐cell ratios. (F) Transitional, naive mature, memory, and double negative (DN; CD27−IgD−) frequencies within total B cells. All data are presented as mean ±SEM and analyzed using Kruskal‐Wallis and Dunn's post hoc tests. Outliers were identified and excluded using Grubbs’ test. *p < 0.05, ***p < 0.001.
FIGURE 2
FIGURE 2
Reduced frequencies of T‐bet+ and CXCR3+ B cells in the blood of people with progressive MS. (A, B) Representative gating and frequencies of T‐bet+ and CXCR3+ populations within total and memory B cells. (C) Antibody‐secreting cell (ASC) frequencies from in vitro‐cultured memory B cells of treatment‐naive people with relapsing and progressive MS (n = 3–6). (D) Correlation plot showing the relation between ex vivo CXCR3 expression on memory B cells and in vitro CXCR3 expression on ASCs. (E) ASC frequencies within fresh blood samples from treatment‐naive people with relapsing (n = 25) and progressive (n = 33) MS. All data are presented as mean ±SEM and analyzed using Kruskal–Wallis and Dunn's post hoc tests (A, B), Mann–Whitney U‐tests (A, B, C, E) or Spearman correlation coefficients (D). Outliers were identified and excluded using Grubbs’ test. *p < 0.05, **p < 0.01.
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References

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