Publications of Faculty of Medicine:MATRIX METALLOPROTEINASES 3, 9 AND TISSUE INHIBITOR METALLOPROTEINASE 1 IN PAIRED SERUM AND SYNOVIAL FLUID SAMPLES OF PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: Abstract

MMP3), gelatinase-B (MMP9) and TMP1 in patients with early RA and to search for a relationship with disease activity and the rate of radiological progression. We measured MMP3, MMP9 and TMP1 levels using an enzyme linked hnmunosorbent assay (ELBA). Paired samples of serum and synovial fluid (SF) were collected from 40 patients with RA presenting with knee effusion and 20 matched healthy subjects as a control group presenting with traumatic non hemorrhagic knee synovial effusion. Radiographs of the hands, wrists and forfeet were taken for all RA patients at baseline and after 2 years. Radiographic damage and scoring were evaluated according to Larsen-Dale index. There were significant elevation in the mean serum and SF levels of MMP3, MMP9 and TDdPl in RA patients at entry hi comparison with the control group (P<0.001) for all comparisons except serum TIMP1 (P<0.05) being 5.7,2.1,1.3 folds higher in serum and 122.3,20.5,17.7 folds higher in the SF. The mean SF levels of MMP3 and TIMP1 in RA patients were significantly higher than their serum levels (P<0.001) being 266 and 12.3 folds higher respectively, as regard the MMP9 there was insignificant difference (P>0.05). The serum and SF levels of MMP3, MMP9 and TIMP1 were significantly increased in higher grades of disease activity (P<0.001). According to Larsen grading at the entry of the study, 15 patients (38%) were grade I and 25 patients (62%) were grade II. There were higher serum MMP3 and higher SF MMP3, MMP9 and TMP1 in patients with higher radiological grade of severity. At the end of the study, 18 RA patients (45%) showed radiological progression, there were highly significant elevations in the mean serum and SF levels of MMP3 (P<0.001) and significant elevation in the mean SF levels MATRIX METALLOPROTEINASES 3, 9 AND TISSUE INHIBITOR METALLOPROTEINASE 1 IN PAIRED SERUM AND SYNOVIAL FLUID SAMPLES OF PATIENTS WITH EARLY RHEUMATOID ARTHRITIS By Yasser, A. Abd El - Hamid; Refaat M. El-Tanawy; Sahar, S. Ganeb; *Khaled, M. Belal and *Hesham, A. Eissa. From Rheumatology & Rehabilitation and 'Clinical Pathology Departments Benha Faculty of Medicine. The Egyptian Rheumatologist, Vol. 28, No. 2, 2006 :P, 293-314 294 Gelatinases degrade the denatured collagen and have also been shown to be associated with the development of radiographic erosion in patients with RA (Goldbach-Mansky et al., 2000). After MMPs are produced and activated their action is further controlled by specific in hibitors of matrix metalloproteinases (TIMPs). Normally, a tight balance exist between MMPs and their tissue inhibitors. However, in patho logical situations such as RA an MMP/nMP imbalance is present, which leads to an excess of activated MMPs which have an important role in the chain of events leading to excessive cartilage degradation (Martel-Pelletier et al., 1994). Aim of the Study: The aim of this study is to determine serum and synovial fluid levels of stromelysin-l (MMP-3), gelatinase-B (MMP-9) and TIMP-1 in patients with early RA and to search for a relationship with disease activity and the rate of radiological progression. Subjects and Methods : This study was carried out at the Rheuma tology and Rehabilitation outpatient clinic and inpatient department of Benha University Hos pitals between September 2003 and September 2005. It included 60 individuals who were di vided into 2 groups: INTRODUCTION: Rheumatoid arthritis (RA) is a chronic and potentially crippling disease characterized by systemic inflammation and joint tissue degra dation. Degradation of articular cartilage is one of the early features of the disease and is medi ated by the increased activity of proteolytic systems (Bresnihan, 1999). Among several en zymes involved in the process, matrix metalloproteinases (MMPs) have been shown to have an important role in the invasion of the synovial tissue in cartilage, cartilage destruc tion and bone erosion formation (Kaneko et al., 2001). Increased levels of MMPs are found in tissue, in the synovial fluid (SF) and in the systemic circulation of patients with RA. Based on the substrate specificity, the family of MMP enzymes is subdivided into subgroups such as stromelysins (MMP-3, -10 and -11), collagenases (MMP-1, -8 and -13), gelatinases (MMP-2, and -9) and membrane-type MMPs (MMP-14, -17, -22, -24, -25) (Nagase and Woessner, 1999). Stromelysins have a wide range of substrate specificity and can also activate other MMPs, thus playing an important role in the MMP cascade (Van Meurs et al., 1999). Pro-MMP-3 levels have been shown to correlate with sys temic inflammatory markers and it was sug gested that they participate in cartilage degra dation (Yamanaka et al., 2000). of MMP9 and TIMP1 (P<0.05) in progressor group. Baseline values of the progressor group showing higher serum and SF levels of MMP3 (P<0.05), (P<0.001) and higher SF levels of MMP9 (P<0.05).