Serum Matrix Metalloproteinase-3 as a Noninvasive Biomarker of Histological Synovitis for Diagnosis of Rheumatoid Arthritis

  • Jian-Da Ma
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Jing-Jing Zhou
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Dong-Hui Zheng
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Le-Feng Chen
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Ying-Qian Mo
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Xiu-ning Wei
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Li-Juan Yang
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China
  • Lie Dai
    Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China

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<jats:p><jats:italic>Objective</jats:italic>. To explore the correlation between matrix metalloproteinase- (MMP-) 3 and histological synovitis in rheumatoid arthritis (RA).<jats:italic>Methods</jats:italic>. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15.<jats:italic>Results</jats:italic>. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenn’s synovitis score<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mfenced separators="|"><mml:mrow><mml:mi>r</mml:mi><mml:mo>=</mml:mo><mml:mn>0.574</mml:mn><mml:mo>,</mml:mo><mml:mi> </mml:mi><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:mfenced></mml:mrow></mml:math>and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mfenced separators="|"><mml:mrow><mml:mi>r</mml:mi><mml:mo>=</mml:mo><mml:mn>0.65</mml:mn><mml:mn>6</mml:mn><mml:mo>,</mml:mo><mml:mi> </mml:mi><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:mfenced></mml:mrow></mml:math>. Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>).<jats:italic>Conclusion</jats:italic>. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.</jats:p>

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