Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital/Children's Hospital, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2022 May 6;13:873644. doi: 10.3389/fimmu.2022.873644. eCollection 2022.
Patients with antiphospholipid syndrome (APS) have immune cell abnormalities that remain poorly understood. This study compared primary APS (PAPS) and secondary APS (SAPS) patients with healthy controls with respect to peripheral blood lymphocytes, CD4+T cell subsets, and cytokine levels. The correlation between antiphospholipid antibody titres and T helper 17 (Th17) and T regulatory (Treg) cell subsets was also analyzed, together with the correlations between cytokine profiles and the clinical characteristics of APS patients.
The retrospective study population consisted of 67 APS patients (12 with PAPS, 55 with SAPS) and 40 healthy controls. Absolute numbers of peripheral blood lymphocyte subsets and CD4+ T cell subsets were detected by flow cytometry, and serum cytokine levels by flow cytometry bead array.
Patients with SAPS had lower absolute values of T, B and CD4+T cells than the healthy control group, while only natural killer (NK) cell levels were decreased in patients with PAPS. Absolute numbers of T, B, NK, and CD4+T cells were significantly higher in the PAPS than SAPS group. The trends in CD4+T cell subsets were the same in PAPS and SAPS patients as in healthy controls, with increased Th1, decreased Th2, and decreased Treg levels, and thus an increased Th17/Treg ratio. Th2, Th17, and Treg cell counts were higher in the PAPS than SAPS group. Cytokine analysis showed that only IL-10 levels differed between the two APS groups. However, the levels of all of the studied cytokines were higher in APS patients than healthy controls, and correlated with the clinical characteristics of the patients. In the PAPS group, the titres of two autoantibodies correlated positively with the Th17/Treg ratio and negatively with the levels of D-dimer and Treg subsets.
Our study clearly showed that APS patients have immune disturbances, the most prominent of which is an increase in the Th17/Treg ratio, due to a decrease in the number of Treg cells. These abnormalities may be involved in the occurrence and progression of APS. An additional finding was a higher level of peripheral blood lymphocytes in PAPS than SAPS patients, which may be related to the immunosuppressive treatment of SAPS patients.
抗磷脂综合征（APS）患者存在免疫细胞异常，但目前仍知之甚少。本研究比较了原发性 APS（PAPS）和继发性 APS（SAPS）患者与健康对照组之间外周血淋巴细胞、CD4+T 细胞亚群和细胞因子水平。还分析了抗磷脂抗体滴度与辅助性 T 细胞 17（Th17）和调节性 T（Treg）细胞亚群之间的相关性，以及细胞因子谱与 APS 患者临床特征之间的相关性。
回顾性研究人群包括 67 名 APS 患者（12 名 PAPS，55 名 SAPS）和 40 名健康对照者。通过流式细胞术检测外周血淋巴细胞亚群和 CD4+T 细胞亚群的绝对数，通过流式细胞术珠阵列检测血清细胞因子水平。
SAPS 患者的 T、B 和 CD4+T 细胞绝对值低于健康对照组，而 PAPS 患者仅 NK 细胞水平降低。PAPS 患者的 T、B、NK 和 CD4+T 细胞绝对值明显高于 SAPS 组。PAPS 和 SAPS 患者的 CD4+T 细胞亚群趋势与健康对照组相同，Th1 增加，Th2 减少，Treg 减少，因此 Th17/Treg 比值增加。PAPS 组的 Th2、Th17 和 Treg 细胞计数高于 SAPS 组。细胞因子分析显示，只有 IL-10 水平在两组 APS 患者之间存在差异。然而，所有研究的细胞因子水平在 APS 患者中均高于健康对照组，且与患者的临床特征相关。在 PAPS 组中，两种自身抗体的滴度与 Th17/Treg 比值呈正相关，与 D-二聚体和 Treg 亚群水平呈负相关。
我们的研究清楚地表明，APS 患者存在免疫紊乱，最明显的是由于 Treg 细胞数量减少导致 Th17/Treg 比值增加。这些异常可能参与了 APS 的发生和发展。另一个发现是 PAPS 患者的外周血淋巴细胞水平高于 SAPS 患者，这可能与 SAPS 患者的免疫抑制治疗有关。
