Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Elevated Expression of MMP9 in Plasma of Patients with Symptomatic Knee Osteoarthritic: Correlation with Disease Severity and Progression.
Attur1, Mukundan, Greenberg2, Jeffrey D., Todd3, John, Lu3, Quynh Ann, Ramirez3, Renita, Oh4, Cheongeun, Samuels1, Jonathan
NYU Hospital for Joint Diseases, New York, NY
New York University School of Medicine, New York, NY
Singulex, Alameda, California, Alameda, CA
New York University, New York, NY
NYU Hospital for Joint Disease, New York, NY
Osteoarthritis is degenerative joint disease that leads to permanent joint damage and is a multi-factorial complex disease. It is well established that in OA cartilage and synovium that some of the metalloproteinases (MMP) are over expressed including MMP- 2, 9 and 13 and Tissue inhibitors of Matrix metalloproteinases (TIMP) are down regulated. There is currently great interest in the field of OA to identify biomarkers that provide a method for earlier diagnosis and identify patients at higher risk for disease progression. This study was designed to test the hypothesis that plasma levels of gelatinase(s) MMP-2 and 9 predict knee OA severity and progression based on radiographic findings.
150 Symptomatic knee OA (SKOA) patients (mean age 63.09 ± 10.3, mean BMI 26.5 ± 3.6) fulfilling ACR criteria for knee OA were recruited as part of an NIH-funded 24 month prospective study. These patients were followed longitudionally for 24 months, x-ray were taken at visit 0 and 24 months. The blood samples were collected at baseline and every 6 months. Standardized semi-flexed radiographs were scored for overall Kellgren and Lawrence (KL) grade, osteophytes, joint space width (JSW) and subchondral sclerosis by the same radiologist. Plasma samples from visit 18 month of 128 OA patients (37% male) were assayed for gelatinase(s) MMP-2 and 9 using the highly sensitive Erenna Immunoassay system (Singulex, Inc). For radiographic severity, biomarker were evaluated between KL scores of 1, 2 with those with scores of 3, 4. Progression of knee OA was defined as a change between baseline and 24 month visit in narrowest joint space width (JSW) in signal knee.
The mean plasma MMP2 and 9 (pro and total) levels were 83.0 ± 63.05 ng/ml, 30.7 ± 32.64 and 455.9 ± 290.09 (all ng/mL), respectively. Only total MMP-9 positively correlated with KL score both at baseline (r=0.220; p<0.036) and 24 (r=0.249; p<0.015) month. MMP-2 or proMMP9 levels did not correlate with either radiographic marker. We further analyzed association of tMMP9 level with radiographic severity and progression by JSN as defined in the methods. tMMP9 correlated with radiographic severity (p<0.061) at baseline, and with progressive joint space narrowing (r= 0.228; p<0.015). However, we did not observe significant association between tMMP9 and delta KL score in this 24 month study.
These findings indicate that elevated levels of total gelatinase -9 (tMMP9) are associated with radiographic severity of SKOA and predict an increased risk of progressive joint space narrowing (JSN). These observations, which suggest that tMMP9 is a candidate prognostic biomarker, merit further validation in larger cohort of SKOA patients.
To cite this abstract, please use the following information:
Attur, Mukundan, Greenberg, Jeffrey D., Todd, John, Lu, Quynh Ann, Ramirez, Renita, Oh, Cheongeun, et al; Elevated Expression of MMP9 in Plasma of Patients with Symptomatic Knee Osteoarthritic: Correlation with Disease Severity and Progression. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1936