| Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterized by inflammatory connective tissue disorder and occurs predominantly in young women. The pathogenetic mechanism of SLE is undefined. Many kinds of adhesion molecules and MMPs may play effects on the pathogenesis of SLE.Matrix Metalloproteinases (MMPs) are members of a family of Zn-dependent endopeptidases that are responsible for degradation of various protein components of the extracellular matrix (ECM). Of the MMPs family, MMP-9 is an important regulator in inflammatory reaction. It play an important role in migration of inflammatory cell and invasion of tumor cells by degrade the basement membranes.CD44 is an adhesion molecule on immunocyte, and mainly participate in adhesion of cell-cell and cell-matrix. The ligand of CD44 molecule is ECM. Of the CD44 molecules, the standardformCD44(CD44std) primarily express on haemo-poietic cell. CD44 play a role in activation of T cells, migration of inflammatory cell and as lymphocyte homing receptor.The infiltration of inflammatory cells, vascular lesions and abnormality of ECM metabolism have been shown in SLE. Thus, MMP-9 and CD44 may also play a role in the pathogenesis of SLE. At the present time, the reseachs of CD44 in SLE were few and the serum levels of MMP-9 in SLE were reported inconsistently. To investigate the role of MMP-9 and CD44std in the pathogenesis of SLE. In this study , serum levels of MMP-9 and soluble standardformCD44(sCD44std) in 67 patients with SLE and 28 healthy controls were measured, and their clinical significances were discussed in this paper.Material and methods1. Clinical data28 healthy controls and 67 patients with SLE were evaluated in this study. All patients fulfilled the American Rheumatism Association 1982 revised criteria for the diagnosisof SLE. The patients included 4 males and 63 females whose age ranged from 15 to 79 with an average of 41.12±16.31(SD) years, duration from 20 days to30 years. 49 patients with active SLE were defined according to the Lupus Activity Criteria Count (LACC). The healthy controls excluded rheumatic disease and tumour, and their age and sex matched that of the patients.2. Laboratory studiesThe serum samples were stored at -40°C until use. Serum levels of MMP-9 and sCD44std were measured by enzyme-linked immunosorbent assay (ELISA). ELISA kits for MMP-9 were purchased from R&D Systems Inc and sCD44std were purchased from Bender MedSystems . Assays were performed according to the manufacturer's instruction.3. Statistical analysis3.1 All data analyses were performed using SPSS 13.0 software.3.2 Serum levels of MMP-9 did not follow a Gaussian distribution, so the results were expressed as median values with the 25-75 centiles (interquartile range). Between group differences were analysed with the non-parametric Mann-Whitney U test. The Wilcoxon rank sum test was used to compare paired groups. Correlations were determined by Spearman's rank order correlation and linear regression after logarithmic transformation.3.3 Serum levels of sCD44std follow a Gaussian distribution, so the results were expressed as mean values with the standard deviation (SD). Differences of independent groups or paired groups were analysed with the T test.. Correlations were determined by Pearson correlation and linear regression were used.3.4. The correlation between serum levels of MMP-9 and sCD44std and diseaseactivity statue were analyzed by Logistic regression. 3.5 P values of less than 0.05 were considered significantResults1. Serum levels of MMP-9 and sCD44std in patients with SLE and healthy controls1.1 Serum levels of MMP-9 in patients with SLE were significantly decreased as compared with controls (p<0.01), and that serum levels of sCD44std in patients were significantly increased as compared with controls (p<0.01).1.2 No correlation was found between serum levels of MMP-9 and sCD44std in patients or controls (r= -0.041,p>0.05; r= -0.157,p>0.05, respectively)2. Influence of disease activity on serum levels of MMP-9 and sCD44stdSerum levels of MMP-9 showed no significant differences between active and inactive patients (p>0.05), but serum levels of sCD44std in patients with active SLE were significantly higher than those of the inactive (p<0.01). Logistic regression analysis suggested that serum levels of sCD44std significantly correlated with the disease activity(OR=1.008,p<0.05), while serum levels of MMP-9 negatively correlated with the disease activity(OR=0.623,p>0.05).3. Relationships between clinical manifestations and serum levels of MMP-9 and sCD44std3.1 Serum levels of MMP-9 did not differ significantly between groups of patients with or without various clinical manifestations; serum levels of sCD44std in groups of patients with pulmonary > cerebral and renal involvement were significantly higher than those of without these clinical manifestations.3.2No correlation was found between serum levels of MMP-9 or sCD44std and age or disease duration. (r=0.211, 0.065, 0.055, -0.207, p>0.05, respectively) 3.3No correlation was found between serum levels of MMP-9 and rations of 24 hour urine protein> endogenous creatinine clearance rate (Ccr)> urinary transferring urinary microalbumin> urinary oti-microglobulin and urinary immunoglobulin G (r= -0.028> -0.063, 0.071, 0.080, 0.058, 10.097,P>0.05, respectively). However, significantly positive correlation between serum levels of sCD44std and rations of 24 hour urine protein urinary transferrim urinary microalbumin and urinary immunoglobulin G werefound (r=0.349,P < O.Ol;r=O.35O, P < 0.01; r=0.217, P <0.05; r=0.366, P < 0.01 ) ,and there was no correlation between serum levels of sCD44std and endogenous creatinine clearance rate (Ccr) or urinary ai-microglobulin ( r= -0.070,P > 0.05 r=0.209, P > 0.05 ) .3. Relationships between autoantibodys and serum levels of MMP-9 and sCD44std in SLE patientsSerum levels of MMP-9 in patients with anti-Sm antidody positive group were significantly lower than those in anti-Sm antidody negative group(p<0.01); serum levels of sCD44std in patients with c-ANCA and RF positive group were significantly higher than those in c-ANCA and RF negative group(p<0.05).4. Relationships between some immunologic parameters and serum levels of MMP-9 and sCD44std in SLE patients5.1 No correlation between serum levels of MMP-9 and ESR^ CRP> serum levels of IgG and C3was found ( r=-0.211,p>0.05; r=0.129,p>0.05;r=-0.131,p>0.05;r=0.179,p>0.05 ) , but there were significantly negative correlation between serum levels of MMP-9 and serum levels of IgM (r=-0.434,p<0.01 ) .5.2 There were significantly positive correlation between serum levels of sCD44std and serum levels of IgM and IgG ( r=0.419,p<0.01,r=0.400,p<0.01 ) ,and negative correlation with C3 levels ( r= -0.327,p<0.01) ,but no significant correlation with ESRandCRP (r=-0.197,p>0.05; r=0.015,p>0.05 ) .5. Influece of therpy on serum levels of MMP-9 and sCD44std in SLE patientsAfter treament for 3 months, serum levels of sCD44std were markedly decreased in 16 patients with SLE (pO.Ol), but MMP-9 levels showed no difference (p>0.05).Conclusions1. Serum levels of MMP-9 in patients with SLE were significantly decreased as compared with controls, but Serum levels of MMP-9 could not completely indicate disease activity. So MMP-9 level was not a sensitive indicator for the disease activity and treatment effect of SLE.Serum levels of sCD44std in patients with SLE were significantly increased as compared with controls ,and serum levels of sCD44std in patients with active SLE were also significantly higher than those of the inactive,and significantly correlated with the disease activity.2. . After treament, serum levels of sCD44std were markedly decreased. So sCD44std level might be used as one of the sensitive indicators for the disease activity and treatment effect of SLE.3. Serum level of sCD44std in patients with SLE elevation might indicate pulmonary ^ cerebral and renal involvement, and serum level of sCD44std might be a early sensitive indicator of renal meruli involvement.4. No correlation was found between serum levels of MMP-9 and sCD44std in patients or controls.
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