PMID- 35967336
OWN - NLM
STAT- MEDLINE
DCOM- 20220816
LR  - 20220824
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the 
      clinical value of matrix metalloproteinase-3.
PG  - 939265
LID - 10.3389/fimmu.2022.939265 [doi]
LID - 939265
AB  - 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.
CI  - Copyright (c) 2022 Liang, Wang, Shang, Wang, Feng, Liu, Gao and Luo.
FAU - Liang, Zhaojun
AU  - Liang Z
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
AD  - Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
FAU - Wang, Nan
AU  - Wang N
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
AD  - Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
FAU - Shang, Lili
AU  - Shang L
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
AD  - Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
FAU - Wang, Yanlin
AU  - Wang Y
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
AD  - Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
FAU - Feng, Min
AU  - Feng M
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
AD  - Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
FAU - Liu, Guangying
AU  - Liu G
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
FAU - Gao, Chong
AU  - Gao C
AD  - Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
FAU - Luo, Jing
AU  - Luo J
AD  - Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi 
      Medical University, Taiyuan, China.
AD  - Shanxi Key Laboratory for Immunomicroecology, Taiyuan, China.
LA  - eng
PT  - Journal Article
DEP - 20220727
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Anti-Citrullinated Protein Antibodies)
RN  - 0 (Autoantibodies)
RN  - 0 (Biomarkers)
RN  - EC 3.4.21.76 (Myeloblastin)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Anti-Citrullinated Protein Antibodies
MH  - *Arthritis, Rheumatoid
MH  - Autoantibodies
MH  - Biomarkers
MH  - Humans
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Myeloblastin
PMC - PMC9363571
OTO - NOTNLM
OT  - anti-citrullinated protein antibodies
OT  - biomarker
OT  - lymphocyte subsets
OT  - matrix metalloproteinase-3
OT  - rheumatoid arthritis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/16 06:00
MHDA- 2022/08/17 06:00
PMCR- 2022/01/01
CRDT- 2022/08/15 03:56
PHST- 2022/05/09 00:00 [received]
PHST- 2022/07/04 00:00 [accepted]
PHST- 2022/08/15 03:56 [entrez]
PHST- 2022/08/16 06:00 [pubmed]
PHST- 2022/08/17 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.939265 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jul 27;13:939265. doi: 10.3389/fimmu.2022.939265. eCollection 
      2022.