Artikel
Loss of balance in circulating autoantibodies targeting CXCR3/CXCR4 and abnormal receptor expression on peripheral blood leukocytes in systemic lupus erythematosus
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Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Aberrant cell migration and chemotaxis are pathophysiological mechanisms underlying vasculopathies in patients with connective tissue diseases such as systemic lupus erythematosus (SLE). In this context, the C-X-C motif chemokine receptor 3 (CXCR3) and 4 (CXCR4), which belong to the G protein-coupled receptors (GPCRs) family, play an essential role during cell migration and chemotaxis. However, their roles in the pathogenesis of SLE remain poorly explored. Our aim was to analyse the concentrations of circulating autoantibodies targeting CXCR3 and CXCR4 receptors, and the expression of these two receptors on peripheral blood leukocytes (PBL) from patients with SLE.
Methods: Anti-CXCR3 and anti-CXCR4 levels in sera from SLE patients (n = 249) were evaluated by ELISA in comparison to healthy controls (n = 198). Moreover, the CXCR3 and CXCR4 expression on peripheral blood leukocyte (PBL) subpopulations such as T helper (CD3+CD4+), T cytotoxic cells (CD3+CD8+), B cells (CD19+), neutrophils (CD15+), and monocytes (CD14+) from patients with SLE (n = 10) were analysed by flow cytometry in comparison to those from healthy controls (n = 10).
Results: Increased anti-CXCR3 and anti-CXCR4 autoantibodies concentrations were identified in SLE. Moreover, PBL subpopulations from SLE patients displayed alterations in CXCR3 and CXCR4 expression patterns. SLE patients demonstrated decreased CXCR3 expression on monocytes and CD4+ T cells, while CXCR4 expression was increased on B and CD4+ T cells.
Conclusion: SLE patients have increased circulating anti-CXCR3 and -CXCR4 antibody levels and abnormal expression of CXCR3 and CXCR4 receptors on PBL underlying SLE pathogenesis. The mechanisms behind and the consequences to these findings remain to be investigated.