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Bruton’s tyrosine kinase activity found in B-cells of patients with RA, pSS
Researchers from the Netherlands found enhanced Bruton’s tyrosine kinase activity in the peripheral blood B lymphocytes of patients with rheumatoid arthritis and in patients with Sjögren’s syndrome, according to results of a recently published study.
“We found increased [Bruton’s tyrosine kinase] BTK levels in subsets of patients suffering from two distinct autoimmune diseases, indicating that disrupted BTK expression is not a unique feature of one disease but may be involved in more autoimmune diseases,” Odilia B.J. Corneth, PhD, in the Department of Pulmonary Medicine at Erasmus MC in the Netherlands, and colleagues wrote. They added, “Our data show a clear link between high BTK expression and autoantibodies, suggesting that autoimmune diseases featuring autoantibody production may be interesting candidates for future studies.”
Corneth and colleagues used intracellular flow cytometry to assess BTK expression and phosphorylation in the peripheral blood B cells of 30 patients with rheumatoid arthritis (RA), 26 patients with primary Sjögren’s Syndrome (pSS) and 41 matched healthy controls.
Researchers found BTK protein expression correlated with BTK phosphorylation; in vitro, BTK expression was unregulated after B cell receptor stimulation and was significantly higher in CD27+ memory B cells than in CD27-lgD+ naïve B cells; and BTK was increased in both naïve and memory B cells and correlated with CCR6+ T helper-17 cell frequency.
In patients with RA, BTK protein and phosphorylated BTK were significantly higher in patients who were anti-citrullinated protein antibody (ACPA)-positive, but not ACPA-negative. In patients with pSS, BTK protein was increased and correlated with serum rheumatoid factor levels. In addition, parotid gland T-cell infiltration and an abatacept target of T-cell activation restored BTK protein expression to normal levels. – by Will Offit
Disclosures: The researchers report no relevant financial disclosures. The study was financially supported by the Dutch Arthritis Foundation. The open-label Active Sjögren Abatacept Pilot (ASAP) study was supported by an unrestricted grant and study medication by Bristol-Myers Squibb, France.