Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix metalloproteinase-3.

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.