Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


High Level of Serum Matrix Metalloproteinase-3 Could Be Implicated in the Pathogenesis of Rheumatoid Interstitial Lung Disease.

Koyama3,  Yoshinobu, Tsuruno1,  Kosuke, Ota2,  Toshiyuki, Fujii1,  Kenji

Center for Rheumatic Diseases, Iizuka Hospital
Department of Laboratory and Transfusion Medicine, University of Occupational and Environmental Health
Iizuka Hospital, Iizuka, Japan

Background:

Pulmonary complications such as interstitial lung disease (ILD) are common in patients with rheumatoid arthritis (RA) even in the absence of symptoms. Presentation of ILD has been reported to associate with seropositive and erosive joint disease. Although the etiology of ILD in RA is still unclear, matrix metalloproteinase (MMP)s are believed to play important roles in the pathogenesis of idiopathic pulmonary fibrosis recently. Among them, MMP-3 is known to be one of the most established markers indicating RA activity. However, the correlation between ILD and level of serum MMP-3 in RA has not been well discussed.

Objectives:

To identify whether serum MMP-3 level has implication for the pathogenesis of ILD in RA.

Methods:

Newly diagnosed RA patients (n=86) were enrolled in this study. As a loss of carbon monoxide diffusing capacity (DLCO) is quantitative and one of the most sensitive marker for ILD, correlations between a loss of DLCO and serum indices for diagnosis of RA were evaluated. Before the patients were exposed to medication, the activity of RA (DAS-28) and the level of laboratory data such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), serum amyloid A protein (SAA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody and %DLCO were evaluated. RA patients were classified in three groups by the %DLCO based on the criteria of the American Thoracic Society (group A; DLCO>70%; normal to slight decrease, group B; 50%<DLCO<70%; moderate decrease, group C; DLCO<50%; severe decrease). Statistical analysis was performed to identify the characteristic pattern of serum markers in the three groups.

Results:

At the time of diagnosis for RA, the titer of RF and anti-CCP antibody seemed to be no significant influence on a loss of DLCO. Although DAS28, CRP or SAA seemed to be no direct impact on %DLCO, a weak association between high ESR and the loss of DLCO was found (P<0.05). The serum level of MMP-3 was the most significant index correlating with a loss of DLCO (P<0.01). The significant negative correlation between MMP-3 and %DLCO was also detected (P<0.05). If the level of MMP-3>=450ng/ml, the relative risk of severe decrease of DLCO (DLCO<50%) was 6.1.

Conclusion:

Although the elevation of inflammatory markers such as ESR or CRP is known to be associated with the elevation of serum MMP-3, we found the MMP-3 was the most significant index correlating with a loss of DLCO. In our study, titer of RF or CCP antibody seems no significant association with rheumatoid ILD at the time of diagnosis for RA. As MMPs are believed to play important roles in the pathogenesis of idiopathic pulmonary fibrosis recently, our finding suggests that MMP-3 is possible to play an important role in the developing of ILD associated with RA. The novel approach such as the correction of inappropriate expression of MMP-3 would be worth to discuss for preventing progression of ILD in RA patients.

To cite this abstract, please use the following information:
Koyama, Yoshinobu, Tsuruno, Kosuke, Ota, Toshiyuki, Fujii, Kenji; High Level of Serum Matrix Metalloproteinase-3 Could Be Implicated in the Pathogenesis of Rheumatoid Interstitial Lung Disease. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1086
DOI: 10.1002/art.28853

Abstract Supplement

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