Abstract

BackgroundAntiphospholipid syndrome (APS) is a typical autoimmune disease, which can be classified into primary antiphospholipid syndrome (PAPS) and secondary antiphospholipid syndrome (SAPS) based on the presence or not of other autoimmune diseases. Disorders of peripheral blood lymphocyte and CD4+T cell subsets, especially Th17 and Treg cell subsets, may be involved in the pathogenesis of APS.ObjectivesTo investigate the differences of peripheral blood lymphocyte and CD4+T cell subsets between patients with primary and secondary antiphospholipid syndrome and healthy controls, and to evaluate the correlation of antiphospholipid antibody titers and Th17/Treg values in PAPS and SAPS groups, as well as the correlation of cytokines and clinical characteristics in APS patients.MethodsA total of 67 APS patients (12 PAPS patients, 55 SAPS patients) and 40 healthy controls were enrolled in this study. Retrospectively collected clinical and laboratory data of these patients. The absolute numbers of peripheral blood lymphocyte subsets and CD4+ T cell subsets were detected by flow cytometry, and serum cytokine levels were detected by flow cytometry bead array.ResultsCompared with healthy control group, the absolute values of T [689.26 vs. 1239.00, p<0.001], B (104.69 vs. 177.50, p<0.001), NK (98.97 vs. 300.00, p<0.001) and CD4+T (330.16 vs. 628.50, p<0.001) cells in SAPS group were decreased. While only the NK cells (151.30 vs. 300.00, p=0.002) in the PAPS group were lower than that in healthy control group. However, the absolute values of T (1295.41 vs. 689.26, p=0.001), B (184.44 vs. 104.69, p=0.012), NK (151.30 vs. 98.97, p=0.023) and CD4+T cells (698.34 vs. 330.16, p=0.002) in PAPS group were significantly higher than those in SAPS group. For CD4+T cell subsets, PAPS patients and SAPS patients showed the same trend compared with healthy controls, showing increased Th1(111.50 vs. 23.47, p=0.002 and 71.43 vs. 23.47, p=0.001, respectively), decreased Th2(6.97vs.12.43, p=0.037 and 2.49 vs. 12.43, p<0.001, respectively) and, more importantly, decreased Treg (18.77 vs. 29.53, p=0.031 and 12.01 vs. 29.53, p<0.001, respectively), with increased Th17/Treg ratio (0.39 vs. 0.17, p=0.001 and 0.42 vs. 0.17, p<0.001, respectively). Meanwhile, Th2(6.97 vs. 2.46, p=0.006), Th17 (8.42 vs. 4.00, p=0.042) and Treg (18.77 vs. 12.01, p=0.020) cells in PAPS group were higher than those in SAPS group. As for the correlation study, we concluded that both aCL (r=0.6061, p=0.0405) and aβ2GPI (r=0.6900, p=0.0158) were positively correlated to Th17/Treg ratio in PAPS group. In addition, for APS patients, IL-2 (r=-0.420, p=0.010), IL-4 (r=-0.392, p=0.016), IL-10 (r=-0.331, p=-0.046), IL-17 (r=-0.479, p=0.006), and IFN-γ (r=-0.339, p=0.040) were negatively correlated with titers of aCL. And IL-6 is also associated with ESR (r=0.469, p=0.004) and CRP (r=0.670, p<0.001).ConclusionWhether PAPS or SAPS patients, detection and balancing of lymphocyte and CD4+T subsets, especially Th17 and Treg subsets, may help correct immune disorders. Of course, the immune function of primary and secondary APS patients is not completely consistent, at least in terms of immune cells. Also, the role of cytokines in the pathogenesis of APS should not be ignored.Figure 1.Comparison of lymphocyte absolute values and CD4+ T cell subsets in PAPS group, SAPS group and healthy control group.Figure 2.The correlation analysis between the value of Th17/Treg and the titer of aCL and aβ2GPI in PAPS group and SAPS group, respectively.Figure 3.Heatmap of correlation of the serum cytokine levels of a variety of cytokines with clinical and laboratory characteristics of APS patients.Disclosure of InterestsNone declared

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