title: Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.
abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19⁺ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD⁺ subsets. Within memory subsets, a higher frequency of CD21⁺ CD38⁻ B cells (> 20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.
authors.affiliation: Department of Rheumatology Research, Division of Medicine, University College of London.
authors.forename: F
authors.initials: F
authors.lastname: Mensah
authors.affiliation: Department of Immunology, Epsom and St Helier University Hospitals NHS Trust.
authors.forename: A
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Department of Neurology, Royal London Hospital of Integrated Medicine, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Berkovitz
authors.affiliation: Department of Rheumatology Research, Division of Medicine, University College of London.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Rheumatology Research, Division of Medicine, University College of London.
authors.forename: V
authors.initials: V
authors.lastname: Reddy
authors.affiliation: Department of Rheumatology Research, Division of Medicine, University College of London.
authors.forename: M J
authors.initials: MJ
authors.lastname: Leandro
authors.affiliation: Department of Rheumatology Research, Division of Medicine, University College of London.
authors.forename: G
authors.initials: G
authors.lastname: Cambridge
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000378:metabolism; D018951:Antigens, CD20 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015415:Biomarkers; D051927:CD24 Antigen / Q000276:immunology; D003430:Cross-Sectional Studies; D015673:Fatigue Syndrome, Chronic / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D017464:Receptors, Complement 3d / Q000276:immunology; D000069283:Rituximab / Q000627:therapeutic use; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D015415:Biomarkers; D051927:CD24 Antigen; C497889:CD24 protein, human; D007072:Immunoglobulin D; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000069283:Rituximab; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
keywords: B cells; chronic fatigue syndrome; flow cytometry; human; myalgic encephalomyelitis