{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:39:52Z","timestamp":1791689992043,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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<jats:sup>+<\/jats:sup> T cell subsets between ACPA<jats:sup>+<\/jats:sup> and ACPA<jats:sup>-<\/jats:sup> RA patients, and to evaluate the value of matrix metalloproteinase-3 (MMP-3) as a diagnostic and monitoring marker in ACA<jats:sup>-<\/jats:sup> RA patients. A total of 145 ACPA<jats:sup>+<\/jats:sup> RA patients, 145 ACPA<jats:sup>-<\/jats:sup> 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<jats:sup>-<\/jats:sup> RA patients, ACPA<jats:sup>+<\/jats:sup> cases had greater imbalances between peripheral CD4<jats:sup>+<\/jats:sup> T cell subsets, mainly manifested as an increase in T-helper 1 (Th1) cells (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) and decrease in regulatory T (Treg) cells (<jats:italic>p<\/jats:italic> = 0.029). This makes these patients more prone to inflammatory reactions and joint erosion. MMP-3 levels in ACPA<jats:sup>+<\/jats:sup> and ACPA<jats:sup>-<\/jats:sup> RA patients were significantly higher than in HCs (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), and MMP-3 could effectively distinguish between ACPA<jats:sup>-<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cell subsets in ACPA<jats:sup>-<\/jats:sup> RA patients. MMP-3 may be used as a potential marker for early diagnosis of ACPA<jats:sup>-<\/jats:sup> RA. MMP-3 was an important index for RA disease evaluation, disease activity stratification, and prognosis.<\/jats:p>","DOI":"10.3389\/fimmu.2022.939265","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T04:41:06Z","timestamp":1658896866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix 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