Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study

Clin Exp Immunol. 2016 May;184(2):237-47. doi: 10.1111/cei.12749. Epub 2016 Feb 22.


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.

Keywords: B cells; chronic fatigue syndrome; flow cytometry; human; myalgic encephalomyelitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD19 / metabolism
  • Antigens, CD20 / immunology
  • B-Lymphocyte Subsets / immunology*
  • Biomarkers
  • CD24 Antigen / immunology
  • Cross-Sectional Studies
  • Fatigue Syndrome, Chronic / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin D / immunology
  • Immunologic Factors / therapeutic use
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Receptors, Complement 3d / immunology
  • Rituximab / therapeutic use
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*
  • Young Adult


  • Antigens, CD19
  • Antigens, CD20
  • Biomarkers
  • CD24 Antigen
  • CD24 protein, human
  • Immunoglobulin D
  • Immunologic Factors
  • Membrane Glycoproteins
  • Receptors, Complement 3d
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Rituximab
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1