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A2.18 Dysregulated BTK expression in peripheral blood B lymphocytes in systemic autoimmune disease
  1. OBJ Corneth1,
  2. MJW de Bruijn1,
  3. SC Bijer-Liefers2,
  4. K de Leeuw2,
  5. FGM Kroese2,
  6. H Bootsma2,
  7. LP Kil1,
  8. RW Hendriks1
  1. 1Department of Pulmonary Medicine, Erasmus MC Rotterdam, The Netherlands
  2. 2Department of Rheumatology and Clinical Immunology, Faculty of Medical Sciences, University of Groningen, The Netherlands

Abstract

Background and objectives 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.

Methods Intracellular BTK expression levels were quantified by intracellular flow cytometry in several peripheral B cell subsets in SLE patients and healthy controls ex vivo and upon stimulation in vitro.

Results 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 in vitro. 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.

Conclusions 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.

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