A2.18 Dysregulated BTK expression in peripheral blood B lymphocytes in systemic autoimmune disease

Abstract

<h3>Background and objectives</h3> Pharmacological inhibition of Bruton’s tyrosine kinase (BTK), which delivers crucial survival signals from the B cell antigen receptor (BCR) in B cells, effectively prevents or ameliorates systemic lupus erythematosus (SLE) and autoimmune arthritis in mouse models. Conversely, increased BTK expression in B cells induces an SLE-like disease phenotype in transgenic mice. Given the crucial role of Btk in murine SLE pathogenesis, in this report we quantified BTK expression levels in human peripheral blood B cells from healthy controls and SLE patients. <h3>Methods</h3> Intracellular BTK expression levels were quantified by intracellular flow cytometry in several peripheral B cell subsets in SLE patients and healthy controls <i>ex vivo</i> and upon stimulation <i>in vitro</i>. <h3>Results</h3> In agreement with previous findings in the mouse, BTK protein expression in naïve B cells from both healthy individuals and SLE patients was upregulated upon BCR stimulation <i>in vitro</i>. When we quantified BTK expression in different peripheral blood subsets in healthy controls, we observed that BTK expression was significantly higher in CD27⁺IgD⁺ non-switched memory B cells than in CD27^-IgD⁺ naive B cells. However, BTK protein levels in non-switched memory B cells from SLE patients were lower compared with healthy controls. Interestingly, we found that the proportions of circulating IgD⁺CD27⁺ non-switched memory B cells, which were previously found to be reduced in SLE patients irrespective of disease activity, inversely correlated with disease duration in SLE patients. <h3>Conclusions</h3> Taken together, this study delivers the first evidence that BTK expression is altered in SLE patients. We are currently studying Btk levels in B cells from patients with other systemic autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.