Association Of CD11b Single Nucleotide Polymorphism With Systemic Lupus Erythematosus In Chinese Han Population

Background Systemic lupus erythematosus(SLE)is a typically autoimmune disease with multisystem organ involvement.It is characterized by immunological defects caused by abnormal immune regulation and excessive production of autoantibodies.The genetic susceptibility is the hallmark of systemic lupus erythematotus.Recent studies found an association between avariant at exon 3(rs1143679)of intergrin CD11b(also called ITGAM)and lupus susceptibility through genome-wide association studies in multiplex SLE families and by case-control studies.In addition,clinical manifestations of lupus patients including renaldisease,discoid rash and autoantibody production were also associated with CD11b gene variant.However,no data are available about the prevalence of rs1143679 in Chinese SLE population.And it is far from clear CD11b mutation leads to the development of SLE.Yanjun,et al.found that CD 11b is critical in regulating B cell(BCR)-mediated autoreative B cell activation/tolerance.Interactions between CDllb and BCR signaling pathway has been determined by animal model and cell level research,and the result has been published on Nature Communications journal.In order to get the verification in clinical SLE patients,we did a cooperation greement with Yanjun research team and got the National Natural Science Foudation project(NO.81228018).We will investigate the single nucleotide polymorphism(SNP)of ITGAM in Chinese Han patients with SLE,and clarify the correlation of ITGAM mutation and specific clinical manifestations of lupus patients.We also will detect the changes of B cell function.This would be help for define the mechanisms of CD11b in the regulation of B cell activation and provide a potential novel therapertic strategy for SLE treatment.Part 1ITGAM single nucleotide polymorphism with systemic lupus erythematosus in Chinese Han populationObjective:to investigate the single nucleotide polymorphism(SNP)of ITGAM in Chinese Han patients with systemic lupus erythematosus(SLE),and clarify the association of this SNP with SLE clinical manifestations.Methods:SNP of ITGAM rs1143679 were conducted in 984 patients with SLE and 928 healthy controls by a polymerase chain reaction-restriction fragments length polymorphism(PCR-RFLP)and direct sequencing in case-control study to compare the frequencies distribution of genotype and allele,and determine the correlation of ITGAM genotypes and clinical manifestations.Result:In this study,we found that(1)the frequency of ITGAM rs113679 A allele in Chinese Han patients with SLE was 1.17%,which was much lower than the frequency of European and American,but close to the frequency of Japanese and Thailand.(2)rs1143679 SNP was associated with SLE susceptibility,nephritis and antiphospholipid(P<0.05),but not associated with malar rash,disoid,photosensitivity,arthritis,hematological involvement,nervous lession and SLEDAI(P>0.05).Conclusion:the ITGAM rs1143679 SNP has risk for SLE in Chinese Han population,and maybe play a important role in the development of lupus nephritis.Part 2Apoptosis and CD11b expression of B cell in SLE with CD11b mutation variantObjective:to explore significance of B cell apoptosis and expression of CD11b in SLE with CD11b mutation variant.Methods:apoptosis rate and expression of CD11b of B lymphocytes in a-cute period and recovered period were measured with flow cytometry in 11 cases of mutation SLE,compared with 11 cases of nonmutation SLE and 11 cases of health control.Results:(1)In acitive period,CD11b of B lymphocytes was(32.6±5.4)%,and of non-mutation group(35.2±6.5)%and is higer than that of control health group(25.6±4.9)%,but no difference was found in mutation and non-mutation(P=0.32).In recovered period,SLE CD11b of B lymphocytes was equal to that of health control,and difference with that acute in period(P<0.01).(2)Apoptosis rate of peripherial blood B lymphocytes in mutation SLE were(15.9±3.5)%in acute period,and(10.5±3.2)%in recovered period,respectively.Both of them were lower than that of non-mutation group(P=0.001).In recovered period of mutation SLE,B cell apoptosis rate decreased whether in mutation or non-mutation SLE patient(P=0.001).Conclusion:CD11b mutation don't change the expression of CDllb moleculer on B cell surface,but decrease the apoptosis rate of B lymphocytes.