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. — CFSMEATLAS
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.
Lunde, Sigrid, Kristoffersen, Einar K, Sapkota, Dipak et al. · PloS one · 2016 · DOI
Quick Summary
Researchers tested whether a drug called rituximab, which removes B cells (a type of immune cell) from the blood, helps ME/CFS patients by examining immune system changes. They found that some ME/CFS patients had higher levels of a substance called BAFF that activates B cells, but this didn't predict who would improve with treatment. While some patients did get better with rituximab in earlier trials, the immune cell changes measured in this study didn't fully explain why.
Why It Matters
This study helps researchers understand how rituximab works in ME/CFS by ruling out certain immune mechanisms, narrowing the focus for future investigations. The finding that B-cell removal improves symptoms without major T-cell or NK-cell changes suggests ME/CFS immune dysfunction involves different mechanisms than previously hypothesized, potentially opening new treatment avenues.
Observed Findings
Baseline serum BAFF was significantly elevated in ME/CFS patients compared to healthy controls (p=0.011)
Baseline IgG levels were significantly lower in rituximab responders compared to non-responders (p=0.03)
T-lymphocyte subsets and T-cell activation markers showed no significant changes over follow-up, between rituximab and placebo groups, or between responders and non-responders
Modest but significant reductions in mean serum immunoglobulins occurred at 24 months: IgG decreased from 10.6 to 9.5 g/L, IgA from 1.8 to 1.5 g/L, and IgM from 0.97 to 0.70 g/L
APRIL serum levels were not significantly different between ME/CFS patients and controls at baseline or during follow-up
Inferred Conclusions
B-cell regulatory effects on T-cell or NK-cell subsets are not the primary mechanisms explaining clinical improvements observed in rituximab trials
The elevated baseline BAFF levels suggest an activated B-lymphocyte system in a subgroup of ME/CFS patients, though this did not predict treatment response
The clinical benefits of rituximab in ME/CFS likely involve mechanisms other than T-cell or NK-cell modulation
Remaining Questions
What are the functional capabilities of the remaining immunoglobulins after B-cell depletion, and do they maintain adequate protective immunity?
What This Study Does Not Prove
This study does not prove that rituximab is effective for all ME/CFS patients—it only describes immune markers in previous trial participants. It also does not establish why rituximab helped some patients, since the measured immune changes didn't correlate with clinical improvement. Finally, the lack of functional antibody assays means the study cannot determine whether remaining immunoglobulins were adequately protective.