Ineffective response to EBV in MS not seen in similar diseases

The aberrant immune response to Epstein-Barr virus (EBV) in MS does not extend to neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and Susac syndrome. The response to EBV is modified by MS treatments interfering with EBV host cells or activated lymphocytes, German researchers found.

MS patients have elevated titers of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Dr Tilman Schneider-Hohendorf (University of Münster, Germany) explained that a preceding study by his group showed that MS is associated with a broader MHC-I-restricted EBV-specific T-cell receptor beta chain (TRB) repertoire than controls [1]. “This can be interpreted as an imprint of an aberrant primary or ongoing ineffective response to EBV in MS.” The researchers wanted to know if the ineffective response to EBV in MS extends to NMOSD, MOGAD, and Susac syndrome [2]. They also evaluated whether this ineffective EBV response can be influenced by MS therapies.

Dr Schneider-Hohendorf and colleagues sequenced blood samples of cohorts with NMOSD, MOGAD, and Susac syndrome who were matched with patients with MS and healthy controls, balanced for age, sex, and HLA alleles. They found that, other than in MS, none of the evaluated diseases presented with a broader anti-EBV TRB repertoire.

Furthermore, modulation of the broader anti-EBV TCR repertoire by ocrelizumab, teriflunomide, and dimethyl fumarate was observed, but not by interferon-beta or glatiramer acetate. None of the DMTs modulated an anti-cytomegalovirus response. Dr Schneider-Hohendorf offered 2 possible explanations for these findings: “Either there is a direct depletion of anti-EBV-specific CD8+ cells; or a more indirect mechanism whereby EBV-infected B cells are depleted in large numbers, and subsequently less of an EBV response is required.”

Future studies will have to demonstrate whether the observed modulation of the EBV response by some of the DMTs directly contributes to their clinical efficacy.

1. Schneider-Hohendorf T, et al. J Exp Med. 2022 Nov 7;219(11):e20220650.
2. Schneider-Hohendorf T, et al. Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation. Abstract O133, ECTRIMS 2024, 17–20 October 2024, Copenhagen, Denmark.

Medical writing support was provided by Michiel Tent

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Posted on 24 September 202424 September 2024