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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1489312
This article is part of the Research Topic Shedding Light on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) View all 5 articles

Deep Sequencing of BCR Heavy Chain Repertoires in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Provisionally accepted
Audrey Ryback Audrey Ryback *Graeme James Macfarlane Cowan Graeme James Macfarlane Cowan
  • University of Edinburgh, Edinburgh, United Kingdom

The final, formatted version of the article will be published soon.

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a common and debilitating chronic illness of unknown aetiology. Chronic infection and autoimmune responses have been proposed as two mechanisms that potentially underlie the pathogenesis of ME/CFS. To explore these disease hypotheses, we characterised the antigen-specific receptors of B cells using adaptive immune receptor repertoire sequencing. We compared the B cell receptor (BCR) repertoires of 25 patients with mild-moderate ME/CFS, 36 patients with severe ME/CFS, 21 healthy controls and 28 patients with Multiple Sclerosis (MS) to identify signatures of infection or autoimmune responses. ME/CFS patients did not display increased clonality or differential somatic hypermutation compared to healthy controls and patients with MS. One of two Immunoglobulin Heavy Variable (IGHV) genes, IGHV3-30, reported to be increased in ME/CFS patients in a previous study, was replicated in patients with mild/moderate disease in our cohort. However, there was no evidence of ongoing adaptive responses in IGHV3-30 repertoires from mild-moderate ME/CFS patients with increased IGHV3-30 usage. There were no detectable repertoire signatures associated with infection or autoimmunity in repertoires from ME/CFS patients, but we observed skewing of the ratio of IgM to IgG BCRs in patients with mild/moderate ME/CFS, a preliminary finding that presents an opportunity for follow-up work.

    Keywords: ME/CFS, BCR repertoire sequencing, AIRRseq, MS, Myalgic encephalomyelitis

    Received: 31 Aug 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Ryback and Cowan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Audrey Ryback, University of Edinburgh, Edinburgh, United Kingdom

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