{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:55:28Z","timestamp":1773280528855,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220095\/Z\/20\/Z"],"award-info":[{"award-number":["220095\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1489312","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T05:11:46Z","timestamp":1739769106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis\/chronic fatigue syndrome"],"prefix":"10.3389","volume":"16","author":[{"given":"Audrey A.","family":"Ryback","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme J. 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