| Objective: Rheumatoid arthritis(RA) is a familiar chronic, systemic and inflammatory disease,in which main clinical features are chronic, symmetric poly-synovium joints and extra-articular lesions and high crippledom rate.The etiological factor and pathogenesis of RA were uncompletely known. It was found that high mobility group protein 1 (HMGB1) as a inflammatory factor played an important role in the pathogenesis of RA in resent years. HMGB1 was mainly secreted by activated monocyte/macrophage,which cluster of differentiation antigen include CD68,CD11b,CD14,CD97 etc. The multiplication of CD68+cells in synovial membrane underlayer of RA was one of the marks on morning pathological changes. The CD68+cells mianly included synovioblast and macrophage,which were transformated by monocyte of peripheral blood. The aim of this study was to investigate the roles of monocyte/macrophage and HMGB1 in the pathogenesis of RA through detecting the level of HMGB1 in serum and synovial fluid and the expression of CD14 and CD68 in preiphral blood mononuclear cells.Methods: Twenty-six RA patients and twenty-five normal controls were chosen. Disease modifying antirheumatic drugs(DMARDs) and biologic agent were never used for the RA group. The diagnosis of RA patients were consistent with American Rheumatology Academy(ARA) rheumatoid arthritis diagnostic criteria of 1987. RF, ESR, CRP, IgA, IgM, IgG, C3, C4 and clinical symptoms of RA patients were recorded. Enzyme linked immunosorbent assay (ELISA) was used to measure the levels of HMGB1 in serum and synovial fluid. Flow cytometric analysis was employed for detecting surface antigen (CD14,CD68) of monocytes in peripheral blood. The correlation coefficients and significances were calculated between HMGB1 level,the percentage of CD14,CD68 and the laboratory parameters of disease activity (RF, CRP).All the data were analyzed by SPSS13.0 for windows statistical software. The mean number±standard deviation ( x±s) was used to express the measurement data. The t test was adopted for comparison between groups. Chi-square test was used for the comparison of the enumeration data. Linear correlation was used to in correlation. P value<0.05 was considered significant.Results:1 The demographic details and traditional parameters of disease activity in RA: In the RA group, the mean disease duration was (23.2±13.6) months, with a mean age of (48.3±16.8) yr, and 6 subjects were male, 20 subjects were female. In normal controls, the mean age was (40.2±15.7) yr, 6 subjects were male, 19 subjects were female. There were no significant difference between the patients and normal subjects in age, gender (P>0.05). In the RA group, the mean RF,ESR and CRP were (480.19±609.01)IU/ml,(68.04±26.80)mm/h and (50.64±42.13) mg/L. In the group of 19 patients with synovial fluid, the mean RF,ESR and CRP were (550.46±684.15)IU/ml, (70.63±24.83) mm/h and (55.26±44.53)mg/L.2 The HMGB1 levels in serum of RA group: The HMGB1 level in serum of RA group was (29.739±23.993)ng/ml, which was significantly higher than normal group (4.063±2.871) ng/ml (P<0.01).3 The HMGB1 levels in synovial fluid of RA group: The HMGB1 level in synovial fluid was(154.402±130.349)ng/ml, which was significantly higher than serum (29.474±24.278) (P<0.01).4 The correlation between serum levels of HMGB1 and laboratory parameters of disease(RF,ESR,CRP,PLT): According to correlation analysis, the HMGB1 levels in serum were positively correlated with RF(r=0.528, P<0.01) and CRP (r=0.548, P<0.01). There were no significant correlation between serum levels of HMGB1 and ESR, PLT (P>0.05).5 The correlation between synovial fluid levels of HMGB1 and laboratory parameters of disease(RF,ESR,CRP,PLT): According to correlation analysis, the HMGB1 levels in synovial fluid were positively correlated with RF (r=0.473, P<0.05). There were no significant correlation between synovial fluid levels of HMGB1 and CRP, ESR, PLT (P>0.05).6 The percentage of CD14+,CD68+ in preiphral blood mononuclear cells of RA group: The percentage of CD14+, CD68+ and CD14+/CD68+ in preiphral blood mononuclear cells of RA group were (86.588±5.965)% ,(3.535±2.519)%,(2.830±2.268)%.There were no significant difference between the percentage of CD14+,CD68+, CD14+/CD68+cells in RA group and normal controls (P>0.05).7 The correlation between the percentage of CD14+,CD68+, CD14+/CD68+ in preiphral blood mononuclear cells of RA and laboratory parameters of disease(RF,ESR,CRP,PLT): According to correlation analysis, there were no significant correlation between percentage of CD14+,CD68+, CD14+/CD68+ in preiphral blood mononuclear cells of RA and RF,CRP, ESR, PLT (P>0.05).Conclusions: 1 The HMGB1 levels in serum significantly increased in patients with RA, and the HMGB1 levels in serum were significantly correlated with RF and CRP. It suggested that HMGB1 as an inflammatory factor might play an important role in the pathogenesis of RA.2 There was higher level of HMGB1 in synovial fluid than in serum, and the HMGB1 levels in synovial fluid were significantly correlated with RF. It suggested that HMGB1 might have relation to pathological changes of synovium of peripheral joint and articular cartilage destructions.3 There was no significant difference between the percentage of CD14+, CD68+, CD14+/CD68+cells in preiphral blood mononuclear cells of RA group and the normal controls.4 The detection of HMGB1 level in serum and synovial fluid, monocyte molecules in peripheral blood might reveal the role of monocyte/macrophage in pathogenesis of RA and provide theory evidence to targeted therapy for RA and the development of new drugs.
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