| Objective: Primary Sj?gren’s syndrome(p SS)is a destructive disease in consequence of autoimmune dysfunction of exocrine glands,featuring dry mouth symptoms and dry eye symptoms clinically,with exocrine glands highly infiltrated by lymphocytes.pSS is a common autoimmune disease which affects more women than men.The prevalence of pSS is about 0.3%~0.7% in China.Patients of pSS can also have multiple systems involved symptoms,such as pulmonary interstitial fibrosis and peripheral neuropathy.The early symptoms of pSS are not specific,which may lead to misdiagnosis and mistreatment.Although the pathogenesis of pSS has not been very clear yet,studies have confirmed that pSS belongs to autoimmune inflammation disease.The immune function disorder is the basic part of the occurrence and development of pSS.By detecting the expression of HMGB1/TLR2 in patients with pSS,and analyzing the correlation between HMGB1/TLR2 expression and each clinical characteristics as well as laboratory markers,this study aims to explore the role of HMGB1/TLR2 in the pathogenesis of p SS.Methods:1 This study included 43 patients,all from Department of Rheumatology,Hebei General Hospital,with the diagnosis of primary Sj?gren’s syndrome during January 2015 to December 2015.20 cases of healthy volunteers were taken as controls.Diagnoses of infection and malignancies had been excluded among all of the participants.2 Flow cytometry(FCM)was used to detect expression of TLR2 on peripheral blood mononuclear cells of all the participants.Enzyme linked immunosorbent assay(ELISA)was used to test the serum levels of HMGB1 of all the participants.Record experimental data.3 Symptoms and physical signs of pSS patients were recorded.The serum anti-SSA antibody 、 anti-SSB antibody 、 Rheumatoid factor(RF)、Anti-nuclear antibody(ANA)、Immunoglobulin G(IgG)、Complements(C3、C4)、Erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)of the experimental group(pSS patients)were detected.4 Pathological grading of labial salivary glands: Biopsy of labial salivary glands was performed meanwhile,and the estimation of the pathological grades of lymphocyte infiltration in labial salivary glands was according to the Chisholm creteria.5 Assessment of disease activity: The disease activity index of pSS patients was assessed according to the 2009 European League Against Rheumatism(EULAR)SS disease assessment index(ESSDAI).6 Using SPSS 13.0 software for Statistical analysis.Results:1 The expression of HMGB1/TLR2 of pSS patients: The serum level of HMGB1 in pSS group was(59.17±15.70)ng/ml,while that in control group was(27.89±19.83)ng/ml.The difference between two groups had statistical significance,P<0.001.The positive expression rate of CD14~+TLR2~+ mononuclear cells in pSS group was(80.33±7.27)%,which was significantly higher than that in control group(68.27±16.68)%,P=0.006.2 Relationship between the expression of HMGB1/TLR2 and systemic damages in pSS patients: The pSS group was devided into two groups,according to the systemic damages assessment.The expression of HMGB1 in patients with systemic damages was(57.99±14.89)ng/ml,while that of patients without systemic damages was(60.53±16.87)ng/ml.The difference of HMGB1 expression between two groups had no statistical significance,P=0.603.The expression of TLR2 in patients with systemic damages was(81.06±7.48)%,while that of patients without systemic damages was(79.31±7.17)%.The difference of TLR2 expression between two groups had no statistical significance,P=0.533.3 Relationship between the expression of HMGB1/TLR2 and the expression of autoantibodies in pSS patients: The expression of HMGB1 had no significant difference between ANA positive group and ANA negative group(P>0.05)、anti-SSA antibody positive group and anti-SSA antibody negative group(P>0.05)、anti-SSB antibody positive group and anti-SSB antibody negative group(P>0.05).The serum level of HMGB1 in RF positive group was(67.11±13.46)ng/ml,which was higher than that in RF negative group(55.34±15.46)ng/ml,P=0.019.The expression of TLR2 had no significant difference between ANA positive group and ANA negative group(P>0.05)、anti-SSB antibody positive group and anti-SSB antibody negative group(P > 0.05).The positive expression rates of CD14~+TLR2~+ mononuclear cells in RF and anti-SSA antibody positive groups were significantly higher than those in RF and anti-SSA antibody negative groups,P=0.001,0.005.4 Correlation between the expression of HMGB1/TLR2 and laboratory markers in pSS patients: The expression of HMGB1 in pSS patients had no correlation with IgG、C3、C4、ESR and CRP levels,r=0.190,-0.017,0.081,0.141,0.019,P>0.05.The expression of TLR2 in pSS patients was positively correlated with IgG level(r=0.577,P=0.001),and had no correlation with C3、C4、ESR and CRP levels,r=0.058,0.113,0.270,0.306,P>0.05.5 Relationship between the expression of HMGB1/TLR2 and pathological grades of labial salivary glands in pSS patients: The expression of HMGB1 in grade Ⅲgroup was(52.68±8.46)ng/ml,while that of grade Ⅳgroup was(60.25±17.72)ng/ml.The difference of HMGB1 expression between two groups had no statistical significance,P=0.317.The expression of TLR2 in grade group was(75.35±2.46)%,while that of grade group Ⅲ Ⅳwas(79.13±6.81)%.The difference of TLR2 expression between two groups had no statistical significance,P=0.077.6 Correlation between the expression of HMGB1/TLR2 and disease activity index(ESSDAI)in pSS patients: In pSS patients,there were positive correlation between the expression of TLR2 and ESSDAI(r=0.621,P<0.001),and there were no correlation between the expression of HMGB1 and ESSDAI(r=0.044,P>0.05).7 Correlation between the expression of HMGB1 and the expression of TLR2 in pSS patients: The serum level of HMGB1 was not correlated with positive expression rate of CD14~+TLR2~+ mononuclear cells in pSS patients,r=0.087,P>0.05.Conclusions:1 In pSS group,the expression of HMGB1/TLR2 were significantly higher than those in control group.Between two groups,the differences had statistical significance,suggesting that HMGB1 and TLR2 might both take part in the pathogenesis of pSS,and probably through HMGB1-TLR2 signaling pathway.2 The expression of HMGB1/TLR2 in RF positive group were higher than those in RF negative group,and the expression of TLR2 in anti-SSA antibody positive group was higher than that in anti-SSA antibody negative group,suggesting that HMGB1/TLR2 might play a role in the production of autoantibodies,especially in the production of RF.3 The expression of TLR2 had positive correlation with ESSDAI and IgG level,suggesting that it was closely related to the disease activity and immunological marker which reflected dysfunction of immune system,so we can consider TLR2 as one of the indicators in evaluation of disease activity. |
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