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

ABSTRACT: 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 (p < 0.001) and decrease in regulatory T (Treg) cells (p = 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 (p < 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.

SUBMITTER: Liang Z

PROVIDER: S-EPMC9363571 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Liang Zhaojun Z Wang Nan N Shang Lili L Wang Yanlin Y Feng Min M Liu Guangying G Gao Chong C Luo Jing J

Frontiers in immunology 20220727

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 m ...[more]

PMID: 35967336

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Project description:Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA-), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA- RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA- RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA- RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA- RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA- RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients' ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics.

Dataset Information

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

Publications

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

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