Matrix Metalloproteinase 3 and Acute Phase Proteins As Markers of Disease Activity and Radiographic Damage in Early Rheumatoid Arthritis

Mahmood MTM Ally¹, Bridget Hodkinson², Pieter W.A Meyer¹, Eustasius Musenge³, Mohammed Tikly⁴ and Ronald Anderson¹, ¹University of Pretoria, Pretoria, South Africa, ²Rheumatology, University of the Witwatersrand, Johannesburg, South Africa, ³University of Witwatersrand, Johannesburg, South Africa, ⁴Rheumatology, Division of Rheumatology, University of the Witwatersrand, Johannesburg, South Africa

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Acute-phase reactants, Biomarkers, matrix metalloproteinase (MMP), radiography and rheumatoid arthritis (RA)

Session Information

Title: Cytokines, Mediators, and Gene Regulation

Session Type: Abstract Submissions (ACR)

Background/Purpose: Although matrix metalloproteinase-3 (MMP-3) is believed to be intimately involved in the immunopathogenesis of rheumatoid arthritis (RA), relatively little is known about its relationships to: i) proven genetic markers of disease susceptibility and biomarkers of immune-mediated tissue damage; and ii) disease activity in early RA in comparison with that of the acute phase reactants, C-reactive protein (CRP) and serum amyloid A (SAA).

Methods: Circulating concentrations of MMP-3 were measured by an ELISA procedure in serum specimens from 128 disease-modifying, anti-inflammatory drug-naïve patients with RA of ≤ 2 years duration. These were correlated with shared epitope (SE) genotype, a spectrum (16) of circulating chemokines/cytokines representative of various types of inflammatory and structural cells, acute phase reactants, autoantibodies, and a cartilage breakdown product (COMP), as well as with clinical indices of disease.

Results: . While no associations with SE genotype were evident, serum MMP-3, which was elevated in 56,25% of patients (p<0,0001), was broadly, albeit variably, correlated with most of the chemokines/cytokines (r values = 0.18 - 0.33, P <0.03 - <0.0001), COMP (r = 0.22, P <0.014), and, most notably, CRP and SAA (respective r values of 0.40 and 0.41, (P <0.0000). In the case of clinical indices, MMP-3 correlated with the simplified disease activity index (SDAI, r = 0.29, P < 0.0001), but not with radiographic changes, erosions or nodulosis. However, the correlations of CRP and SAA with SDAI were stronger (respective values of 0.63 and 0.54, P <0.001 for both).

Conclusion: In early RA, MMP-3 is significantly associated with disease activity, inflammatory mediators and cartilage breakdown, and is a potential biomarker of disease severity, but is less useful than CRP and SAA in early RA.

Disclosure:

M. M. Ally,
None;

B. Hodkinson,
None;

P. W. A. Meyer,
None;

E. Musenge,
None;

M. Tikly,
None;

R. Anderson,
None.

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