Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
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+CD25int/highCD45RA+CD127low) 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.
To cite this abstract in AMA style:Hisada R, Kato M, Nakagawa H, Sugawara E, Kanda M, Ohmura K, Nakagawa I, Oku K, Bohgaki T, Amengual O, Horita T, Yasuda S, Atsumi T. Deviation of T and B Cell Subset and Its Association with Single Nucleotide Polymorphisms in Patients with Antiphospholipid Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/deviation-of-t-and-b-cell-subset-and-its-association-with-single-nucleotide-polymorphisms-in-patients-with-antiphospholipid-syndrome/. Accessed August 4, 2021.
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