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Researchers develop metric to measure B cells that drive RA disease
Researchers developed a metric that measures the anti-citrullinated protein memory B cells which drive disease in patients with rheumatoid arthritis, according to a recently published study.
“We developed a simple metric to measure the frequency of pathological autoimmune B cells that initiate and drive the disease process in patients with [rheumatoid arthritis] RA,” Gregg J. Silverman, MD, in the Department of Medicine at New York University School of Medicine, told Healio Rheumatology.
Silverman and colleagues assessed the presence of defects in immune homeostasis as a function of disease activity in patients with RA. Researchers characterized fine-binding antibody-specificities in sera, synovial fluid (SF) and B-cell culture supernatants. They determined the frequency and epitope reactivity pattern of the anti-citrullinated protein antibodies (ACPA) generated by synovial fluid B cells and switched-memory blood B cells. They compared switched-memory blood B cell-generated ACPA to disease activity scores and to ACPA serum levels.
Researchers found SF B cells spontaneously secreted ACPA and constitutive IgG-autoantibody production by peripheral blood mononuclear cells (PBMCs) was less frequent. After in-vitro stimulation, PBMCs secreted the IgG ACPA from switch-based memory B-cells for all patient groups treated with methotrexate. In addition, frequencies of switched-memory ACPA-producing B cells correlated with serum IgG anti-cyclic citrullinated peptide-3 (r = 0.57). Overall, treatment-induced remission had little effect on circulated burden of switched-memory ACPA-producing B cells, which may explain the dysregulation of humoral immunity, researchers wrote.
They concluded a clinical disease activity score is not reliable for determining the resolution of pathogenic recirculating B-cell autoimmunity.
“We hope to use this tool to develop more effective regimens and new agents that will can induce drug-free remission,” Silverman said. – by Will Offit
Disclosure: The researchers report no relevant financial disclosures.