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The Expression Of CXCL12and CXCR4in The Peripheral Blood And It’s T Lymphocytes Of The Patients With Primary Sjogren’s Syndrome

Posted on:2015-03-26Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q ChenFull Text:PDF
GTID:2254330428474153Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:Primary Sjogren’s syndrome(pSS) is a kind of systemicchronic inflammatory autoimmune disease with the characteristics oflymphocyte infiltration in the exocrine glands and occurrence of varieties ofantoantibodies in the peripheral blood.The disease mainly violates theexocrine glands and can affects many other organs,therefore which oftenshows multisystem damage and has a variety of clinical manifestations. Theprevalence rate of pSS is about0.29%~0.77%in China.It is a frequentlyencountered and common disease which severely harms to human health.Thepathogenesis of the disease has been not clear yet.The study on the cytokinesin the pathogenesis of primary sjogren’s syndrome is a hot topic, which mainlyfocuses on the gamma interferon,IL-6,IL-17, TNF alpha and other fields.Thereports about the roles of CXCL12/CXCR4in pathogenesis of pSS isrelatively infrequent.By detecting the expression of CXCL12/CXCR4inpatients with primary Sjogren’s syndrome,this study aims to analyze thecorrelation of the CXCL12/CXCR4expression with the autoantibodies,thepathological grades of labial salivary gland and the disease activity index,tofurther understand the pathogenesis of sjogren’s syndrome in order to providetheoretical basis for treatment.Methods:1The experimental group consisted of30pSS patients, who werecollected at Department of Rheumatology and Clinical Immunology in HebeiProvincal People’s Hospital from May2013to January2014.All patients werefitted with the2002SS international diagnosis (classification) criteria.30casesof normal healthy individuals were taken as controls.2Flow cytometry (FCM) was used to detect expression of CXCR4onperipheral blood T lyphocyte, Enzyme linked immunosorbent assay (ELISA) was used to test the serum levels of CXCR12. The expression ofCXCR4mRNA was measured by qRT-PCR(quantitative Reverse TranscriPtase Polymerase Chain Reaction).3The serum anti-SSA antibody and anti-SSB antibody of patients weredetected by the Western blot.The serum rheumatoid factor(RF) of patients wasdetected by the nephelometry.The serum antinuclear antibody (ANA)ofpatients was detected by immumofluorescence method.Assessment of thedisease activity index of the pSS patients was according to the pSS diseaseassessment index (ESSDAI), which was established by the European Leagueagaist Rheumatism (EULAR) in2009.5The pathological grades of labial salivary glands: Labial salivary glandswere fixed,embedded,sectioned and stained by HE. The estimation of thepathological grades of lymphocyte infiltration in labial salivary glands wasaccording to the Chisholm creteria.6Using SPSS19.0software for statistical analysis.Results:1The expression CXCR12level in patients with pSS:The expressionlevel of the CXCL12in pSS group was411.0﹙337.2,481.5﹚pg/ml,whilethat in healthy control group was72.0﹙63.5,94.0﹚pg/ml. The differencebetween the two groups had statistical significance (P <0.001).2The CXCR4expression on T lymphocytes of pSS patients: The rateCD3+CXCR4+lymphocytes in the group of pSS patients was21.0(16.9,26.0)%,which was significantly higher than that in the group of healthyindividauls4.7(3.25,6.0)%(P<0.001).3The relative number of CXCR4mRNA expression in PBMCs of pSSpatients:The relative number of CXCR4mRNA were8.05(6.76,9.31)and2.13(1.56,2.68)respectively in the groups of pSS patients and healthyindividuals, The difference between two group had statistical significance(P<0.05).4The correlation of CXCL12/CXCR4expression with autoantibodiesexisted in the blood of patients with Sjogren’s syndrome: In the pSS group, there were18cases with ANA positive,13cases anti-SSA positive,18casesanti-SSB positive,24cases RF positive.We divided the30cases of pSS intotwo groups, the antibody positive group with at least one antibody positive andthe antibody negative group with no antibody positive. The CXCL12expression in antibody positive group was415.5(376.8,481.5)pg/ml, whichwas a little higher than that in antibody negative group379.9(236.5,486.8)pg/ml.But the difference between the two groups had no statisticalsignificance(P>0.05).The CXCR4expression in antibody positive group was﹙23.0±5.1﹚%,which was a little higher than that in antibody negativegroup﹙20.0±4.6﹚%. But the difference between the two groups also had nostatistical significance(P>0.05).5The relationship between CXCL12/CXCR4expression and thepathological grades of labial salivary glands in pSS patients: In the pSS group,there were17cases with grade4of pathological grade of labial salivaryglands, while the level of CXCL12expression was﹙401.59±92.40﹚pg/mland there were13cases grade3of pathological grade of labial salivary glands,while the level of CXCL12expression was﹙396.15±123.30﹚pg/ml.Thedifference of the CXCL12expression between the two groups had nostatistical significance(P>0.05). The rates of CXCR4positive expressionwere﹙21.41±4.97﹚%and﹙22.35±5.34﹚%respectively in grade4anggrade3, but the difference of the CXCR4expression between the two gradeshad no statistical significance(P>0.05).6The relationship between CXCL12/CXCR4expression and the diseaseactivity in pSS patients: The disease activity of pSS patients was divided intofour grades according to ESSDAI, score0-2defined as grade1,3-5grade2,6-8grade3,≥9points grade4. The numbers of the patients were12,7,6and5respectively from grade1to grade4. The levels of CXCL12expression inperipheral blood were432.0(361.3,500.5)pg/ml,386.0(233.0,386.0)pg/ml,412.0(360.5,538.5)pg/ml,377.0(342.5,419.0)pg/ml respectively. The ratesof CD+CXCR4+T lymphocytes were21.5(17.0,26.6)%,18.1(15.8,18.1)%,22.9(19.4,22.9)%and22.0(15.4,20.2)%respectively. The expression of CXCL12/CXCR4had no significant difference among different gades ofESSDAI (P>0.05).Conclusions:1.The expressions of CXCL12in peripheral blood, CXCR4on peripheralblood T lymphocytes and the relative number of CXCR4mRNA in peripheralblood mononuclear cells of pSS patients were increased. these suggestedthat CXCL12/CXCR4played a important role in the occurrence anddevelopment of pSS.2.There were no differences in the levels of CXCL12/CXCR4expressionbetween antibody positive group and antibody negative group of pSS patiens.These prompted that the expression of CXCL12/CXCR4in pSS patients hadnothing to do with the production of autoantibody.3.The expression of CXCL12/CXCR4made no difference with thepathological grades of labial salivary glands and the ESSDAI. The correlationof CXCL12/CXCR4expression with the lyphocyte infiltration in the labialsalivary glands and the disease activity had not been found in pSS patients....
Keywords/Search Tags:Primary Sjogren’s syndrome, CXCL12, CXCR4, Anti-SSAantibody, Anti-SSB antibody, RF, ANA, Pathological grades of labial salivaryglands, ESSDAI
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