Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome
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...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1489312/full |
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| author | Audrey A. Ryback Graeme J. M. Cowan |
| author_facet | Audrey A. Ryback Graeme J. M. Cowan |
| author_sort | Audrey A. Ryback |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-44bac156be3b429ca16a48bdfee63e07 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-44bac156be3b429ca16a48bdfee63e072025-08-20T02:13:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14893121489312Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndromeAudrey A. RybackGraeme J. M. CowanMyalgic 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1489312/fullME/CFSBCR repertoire sequencingAIRRseqMSmyalgic encephalomyelitis |
| spellingShingle | Audrey A. Ryback Graeme J. M. Cowan Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome Frontiers in Immunology ME/CFS BCR repertoire sequencing AIRRseq MS myalgic encephalomyelitis |
| title | Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome |
| title_full | Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome |
| title_fullStr | Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome |
| title_full_unstemmed | Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome |
| title_short | Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome |
| title_sort | deep sequencing of bcr heavy chain repertoires in myalgic encephalomyelitis chronic fatigue syndrome |
| topic | ME/CFS BCR repertoire sequencing AIRRseq MS myalgic encephalomyelitis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1489312/full |
| work_keys_str_mv | AT audreyaryback deepsequencingofbcrheavychainrepertoiresinmyalgicencephalomyelitischronicfatiguesyndrome AT graemejmcowan deepsequencingofbcrheavychainrepertoiresinmyalgicencephalomyelitischronicfatiguesyndrome |