Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using Rituximab in MECFS 2016 Lunde Fluge

Jaybee00

Senior Member (Voting Rights)
Lunde S, Kristoffersen EK, Sapkota D, Risa K, Dahl O, Bruland O, et al. (2016) 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. PLoS ONE 11(8): e0161226. doi:10.1371/journal.pone.0161226


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.


I don’t think this article was ever posted on here with its own thread.

Was there ever follow up with BAFF finding?
 
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Looking very briefly at the literature for lupus, it doesn't look as though levels are much higher in lupus as compared to controls or reliably higher at the individual level, although population mean levels are generally higher than controls. 'Elevated BAFF levels have been linked to specific disease features (of lupus), such as renal activity and premature atherosclerosis in some studies.'

AI said 'in SLE.. reported mean levels varying significantly across studies and patient populations. For instance, one study found a mean of 820 ± 40 pg/mL in SLE patients, while another reported a median of 980 pg/mL.'
Those levels don't look very different to the levels reported for ME/CFS and controls in the study this thread is about.

I think the skew to higher in ME/CFS is interesting, something to remember. But, levels didn't change in the ME/CFS group with an improvement in symptoms after rituximab treatment. So, if there is a real difference, it seems to be an underlying tendency that perhaps predisposes to ME/CFS if other conditions are met.

Of course I'd be interested to see if belimumab helped people with ME/CFS, as it is reported to do for people with lupus (I haven't looked to see how real that effect in lupus is). But, it is an immune suppressant, it seems to be a drug with significant risks, especially if added to a treatment regime that also suppresses the immune system.
 
Distinguishing features of Long COVID identified through immune profiling (2023) showed elevated APRIL. They didn't highlight BAFF but it is in the supplementary raw data so presumably was not significantly different. (They also put a lot of emphasis on a low cortisol finding).

Screenshot 2025-08-24 at 8.48.17 AM copy.jpg

FWIW 934 - Evidence of B-Cell Dysfunction in Individuals With Long COVID-Associated Dysautonomia (Poster) showed reduced levels of BAFF and APRIL in a small cohort of patients with dysautonomia (so not necessarily ME/CFS).

BLyS is an alternative name for BAFF. The poster repeats their BLyS graph instead of the APRIL data but the text says also a small negative change (-1.2-fold; p=0.0342).

Screenshot 2025-08-24 at 8.37.23 AM copy.jpg
 
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