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Investigation Of Apoptosis In The Pathogenesis Of Ankylosing Spondylitis

Posted on:2009-12-22Degree:MasterType:Thesis
Country:ChinaCandidate:Y J LiuFull Text:PDF
GTID:2144360245484447Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:Apoptosis is related to the pathological inf- lammation of various autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus(SLE), systemic sclerosis (SSc)etc. Ankylosing spondylitis(AS)is considered as an immune-associated chronic inflammatorydisease, it is not identified whether apoptosis is involved in its pathogenesis.The objective is to explore the relationship between apoptosis with ankylosing spondylitis through the levels of cell apoptosis- related factors TRAIL, sFas and FasL.Methods: 50 patients including 30 cases of AS with knee effusion, 20 cases of RA and 20 cases of normal controls were chosen. All patients were initially treated and never took DMARDs. Serum was taken from all the patients and normal controls,synovial fluid was taken from patients with AS. The onset locations and detections of sacroiliitis by computed tomography(CT) of patients with AS were recorded. Blood was taken for determination of HLA-B27, ESR, CRP and so on.Enzyme linked immunosorbent assay(ELISA) was used to measure the levels of sFas and TRAIL in serum and synovial fluid, sFas and TRAIL levels were made statistical analysis. Three-color flow cytometric analysis was employed for surface antigens(CD3, CD8) of T cells and surface expression of FasL. The correlation coefficients and significances were calculated between sFas (or TRAIL, FasL) and laboratory parameters of disease activity(ESR, CRP).SAS8.0 was used to process all data. Quantitative data were expressed as ( x±s). t-test was used for group com- parition. P values <0.05 were considered significant.Results:1 The demographic details and traditional para- meters of disease activity in AS:In the group of 30 patients with AS, every patients had peripheral arthritis, the mean disease duration at presentation was (13.77±7.06)months, with a mean age of (23.6±5.31)yr, 18 subjects were male, 12 subjects were female, 25 subjects were HLA-B27 positive, 5 subjects were HLA-B27 negative. In 20 normal controls, with a mean age of (24.47±5.73)yr, 12 subjects were male, 8 subjects were female. In the group of 20patients with RA, the mean disease duration at presentation was (11.05±5.27)months, with a mean age of (37.1±12.48), 12 subjects were male, 8 subjects were female. There were no differences between AS group and normal group in age and gender (P>0.05). In the group of 30 patients with AS, ESR(56.6±17.19)mm/h, CRP(35.4±15.76)mg/L, according to the detections of sacroiliitis by CT, 20 subjects with sac- roiliitis displayed gradeⅡbilateral, 6 subjects displayed gradeⅢbilateral, 3 subjects displayed gradeⅢunilateral,1 subjects displayed gradeⅣof unilateral.2 The serum levels of TRAIL and sFas in different groups: The levels of sFas in serum of AS[(3.61±0.72)ng/mL] and RA [(3.55±0.56) ng/mL] were all significantly higher than normal group [(2.68±0.48)ng/mL (P<0.01)]. There were not statistically different between the levels of sFas in AS and in RA. The levels of TRAIL in serum were significantly lower in AS than in normal group and RA (P<0.05). There were not statistically different between the levels of TRAIL in RA and normal group.3 Synovial fluid levels of TRAIL and sFas in AS: The level of sFas in synovial fluid[(4.40±0.82)ng/mL] was significantly higher than in serum(P<0.05). And there were not statistically different between the levels of TRAIL in synovial fluid [(30.24±12.74)pg/mL] and in serum (P>0.05).4 The percentage of CD3+CD8+T cells in peripheral blood lymphocytes of AS group was (25.8±7.17) %. And it was significantly higher than in normal grpoup (18.45±6.41) % (P<0.05). The proportionality of CD3+CD8+CD178+ [(1.79±0.83)℅] in peripheral blood of AS was significantly higher than in normal group(0.88±0.36)% (P<0.01).5 The correlation between serum level of TRAIL(or sFas) and laboratory parameters of disease activity(ESR, CRP): Accor- ding to correlation analysis , serum level of sFas was significiently correlated with ESR and CRP(r=0.4929, 0.5001, P<0.01);There weren no significant correlation between the level of TRAIL and ESR, CRP (P>0.05).6 The positive rate of AS patients of CD3+CD8+T cells surface expression of FasL associated with the lab indicators: According to correlation analysis, the percentage of the expression surface of FasL in peripheral bloodCD3+CD8+Tcells was a positive correlation with ESR and CRP(r =0.6372, 0.5165, P<0.01).Conclusion:1 Serum levels of sFas increased significantly in patients with AS, and the level of TRAIL was lower than normal.The disorder of immune function really existed in the AS patients. TRAIL and sFas may played roles in the pathogenesis of AS. There was a high level of sFas in RA group also.2 There was higher level of sFas in synovial fluid than in serum, it suggests that sFas may has relation to pathological changes of synovium of peripheral joint and articular cartilage destructions. But the level of TRAIL in synovial fluid was no significant difference from serum.3 The surface expression of FasL in CD3+ CD8+ T cells ofAS was significantly higher than normal group, and it sug-gested that FasL may play a role in the pathogenesis of AS.4 sFas serum level significantly increased, and had correlation with laboratory parameters of disease activity(ESR, CRP), that could provide references to the monitoring of pathogenetic conditions of patients with AS.5 The test of serum apoptosis-related factors may provide theory evidence to the use of biological agents for AS and the development of new drugs.
Keywords/Search Tags:Spondylitis, Ankylosing, sFas, FasL, TRAIL, Lymphocytes, Cytokines, Flow cytometry
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