Background/Purpose: Antiphospholipid syndrome (APS) is a well-characterized autoimmune and thrombotic disorder but its pathogenesis remains to be elucidated. Genomic studies have revealed the association of signal transducer and activator of transcription 4 (STAT4) and B lymphoid kinase (BLK) with APS, suggesting the involvement of T cell differentiation and B cell maturation in the development of APS. However, little information has been available on the role of T and B cells in the pathogenesis of APS. We aimed to identify the deviation of lymphocyte subset and its association with single nucleotide polymorphisms (SNPs) in APS patients.

Methods: This cross-sectional study included patients with primary APS (PAPS), APS associated with systemic lupus erythematosus (SLE/APS) and healthy controls. Peripheral blood mononuclear cells and genomic DNA were obtained from these subjects. T cells were analyzed into 12 subsets with markers as follows; CD3, CD4, CD25, CD45RA, CD127, CD45RA, CCR6, CCR7, CXCR3, CXCR5. B cells were analyzed into 6 subsets with markers as follows; CD3, CD4, CD24, CD27, CD38, IgD. In addition, a total of 28 SNPs, which had been shown to associate either with SLE or with thrombotic diseases, were analyzed by TaqMan genotyping assay.

Results: Seventeen PAPS, eight SLE/APS patients and eight healthy controls were included in this study. In T cell analysis, Th2 cells (CD3⁺CD4⁺CD45RA^–CCR6^–CXCR3^–CXCR5^–) were increased in PAPS (p = 0.016, Dunnett’s test) and SLE/APS (p = 0.013) patients compared to healthy controls. Resting regulatory T cells (CD4⁺CD25^int/highCD45RA⁺CD127^low) were decreased in PAPS patients compared to healthy controls (p = 0.017). In B cell analysis, pre-switched memory B cells (CD3^–CD19⁺ CD27⁺IgD⁺) and post-switched memory B cells (CD3^–CD19⁺CD27⁺IgD^–) were simultaneously decreased in PAPS patients compared to healthy controls (p = 0.022 and p = 0.016, respectively). In SNPs analysis, one of Toll-like receptor 7 gene polymorphisms (rs3853839) was associated with the decrease of post-switched memory B cells observed in PAPS patients (p = 0.038).

Conclusion: In APS patients, Th2 cells were increased while resting regulatory T cells, pre- and post-switched memory B cells were decreased. Furthermore, association between Toll-like receptor 7 and a decrease of memory B cells was found in APS patients. The deviation in lymphocyte subsets in patients with APS could be, in part, immunogenetically regulated, presumably contributing to the development of this syndrome.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/deviation-of-t-and-b-cell-subset-and-its-association-with-single-nucleotide-polymorphisms-in-patients-with-antiphospholipid-syndrome/