Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
Front Immunol. 2022 Jul 27;13:939265. doi: 10.3389/fimmu.2022.939265. eCollection 2022.
Anti-citrullinated protein antibodies (ACPAs) are highly specific for the diagnosis of rheumatoid arthritis (RA). However, about one-third of RA patients are negative for ACPAs, which presents a challenge to the early diagnosis of RA. The purpose of this study was to analyze differences in lymphocyte subsets and CD4 T cell subsets between ACPA and ACPA RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA RA patients. A total of 145 ACPA RA patients, 145 ACPA RA patients, and 38 healthy controls (HCs) were included in this study. Peripheral lymphocyte subsets were detected using flow cytometry, and serum MMP-3 was detected using chemiluminescence. Information about joint symptoms, other organ involvement, and related inflammatory markers was also collected. The results showed that, compared to ACPA RA patients, ACPA cases had greater imbalances between peripheral CD4 T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells ( < 0.001) and decrease in regulatory T (Treg) cells ( = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA and ACPA RA patients were significantly higher than in HCs ( < 0.001), and MMP-3 could effectively distinguish between ACPA RA patients and HCs (area under the curve [AUC] = 0.930, sensitivity 84.14%, specificity 92.11%). MMP-3 was also a serum marker for distinguishing between RA patients with low and high disease activities. Further analysis showed that MMP-3 was positively correlated with the levels of inflammatory markers and disease activity, and negatively correlated with the levels of lymphocyte subsets. In addition, with improvements in the disease, MMP-3 levels decreased, and further increased as the patients started to deteriorate. In summary, our research showed that there was a mild imbalance between peripheral CD4 T cell subsets in ACPA RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.
抗环瓜氨酸肽抗体（ACPA）对类风湿关节炎（RA）的诊断具有高度特异性。然而，大约三分之一的 RA 患者 ACPA 为阴性，这给 RA 的早期诊断带来了挑战。本研究旨在分析 ACPA 和 ACPA RA 患者之间淋巴细胞亚群和 CD4 T 细胞亚群的差异，并评估基质金属蛋白酶-3（MMP-3）作为 ACA RA 患者诊断和监测标志物的价值。共纳入 145 例 ACPA RA 患者、145 例 ACPA RA 患者和 38 例健康对照者（HCs）。采用流式细胞术检测外周血淋巴细胞亚群，采用化学发光法检测血清 MMP-3。同时收集关节症状、其他器官受累及相关炎症标志物等信息。结果显示，与 ACPA RA 患者相比，ACPA 患者外周血 CD4 T 细胞亚群失衡更为明显，主要表现为辅助性 T 细胞 1（Th1）细胞增加（ < 0.001），调节性 T（Treg）细胞减少（ = 0.029）。这使得这些患者更容易发生炎症反应和关节侵蚀。ACPA 和 ACPA RA 患者的 MMP-3 水平明显高于 HCs（ < 0.001），MMP-3 可有效区分 ACPA RA 患者和 HCs（曲线下面积[AUC] = 0.930，灵敏度 84.14%，特异性 92.11%）。MMP-3 也是区分 RA 患者低疾病活动度和高疾病活动度的血清标志物。进一步分析显示，MMP-3 与炎症标志物和疾病活动度呈正相关，与淋巴细胞亚群呈负相关。此外，随着病情的改善，MMP-3 水平降低，当病情恶化时进一步升高。综上所述，本研究表明 ACPA RA 患者外周血 CD4 T 细胞亚群存在轻度失衡。MMP-3 可能作为 ACPA RA 的早期诊断潜在标志物。MMP-3 是 RA 疾病评估、疾病活动分层和预后的重要指标。
