Serum BAFF and APRIL levels, T-lymphocyte subsets, and immunoglobulins after B-cell depletion using the monoclonal anti-CD20 antibody rituximab in myalgic encephalopathy/chronic fatigue syndrome
Open accessAbstract
Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6-9.5 g/L, IgA 1.8-1.5 g/L, and IgM 0.97-0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B-cell regulatory effects on T-cell or NK-cell subsets are not the main mechanisms for the observed improvements in ME/CFS symptoms observed in the two previous trials. The modest increase in serum BAFF levels at baseline may indicate an activated B-lymphocyte system in a subgroup of ME/CFS patients.
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B cell depletion by Rituximab has been deployed in clinical trials and has seen some success in treating ME/CFS.
“With immune B cells serving as a reservoir for latent EBV infection, B cell depletion by Rituximab has also been deployed in clinical trials and has seen some success in treating ME/CFS13.”
From Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically-relevant Phenotyping of Women with Chronic Fatigue Syndrome (2019) · cites this paper as [13]
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- Authors
- Lunde, S., Kristoffersen, E. K., Sapkota, D., Risa, K., Dahl, O., Bruland, O., Mella, O., & Fluge, Ø.
- Affiliations
- Haukeland University Hospital (NO)
- Corresponding author
- Fluge, Øystein
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-08-18
- Volume
- 11
- Issue
- 8
- Pages
- e0161226
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4990178
- OpenAlex
- W2508930692
- Cited by
- 22
- References
- 56
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 4 · 2018: 6 · 2017: 6
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- The Kavli Foundation
- Associated Western Universities (US)Norway Regional Health Authority (911557)
- Legal of Torstein Hereid
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- rituximab, B-cell depletion, BAFF, APRIL, T cell subsets, immunoglobulins, serum cytokines, treatment response, maintenance therapy, B cell regulation, T cell activation markers, natural killer cells, anti-CD20 monoclonal antibody, immunophenotyping, IgG, IgA
- MeSH terms
- Rituximab, Adult, B-Lymphocytes, DNA-Binding Proteins, Female, Flow Cytometry, Humans, Immunoglobulins, Immunologic Factors, Male, Transcription Factors, Fatigue Syndrome, Chronic, Case-Control Studies, T-Lymphocyte Subsets, B-Cell Activating Factor
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