| Background Systemic Lupus Erythematosus (SLE) is a typical kind of autoimmunedisease, which can often involve multiple systems and organs, it’s clinicalmanifestations are complex. SLE occurs in young women, especially those reproductivewomen of age between twenty to forty years old. At present, the pathogenesis is still notclear, it is generally thought that the genetic factors and environmental factors, leadingto T cells, B cells and dendritic cell dysfunction and a large number of autoantibodyproduct formation. So far, SLE is still have no special treatment, only thorough study onits pathogenesis, there is hope to find more effective treatment strategies.In recent years, studies have found that the abnormal T helper (Th) cell secretion ofcytokines is related to SLE pathogenes, the traditional CD4+effect of T lymphocyte isdivided into two categories: Thl and Th2, but recent research shows that, according tothe development of cells, function of cells and secretory cell factor are different, the roleof CD4+effective lymphatic cells should be divided into Thl, Th2, Treg and Th17subsets. IL-9was first to be considered as a kind of T cell growth factor.Recentliteratures point out that Thl, Th2, Treg and Th17are the sourse of IL-9, in addition,mast cells and NTK can also produce IL-9.The research of KOICHI YANABA.et al shows that the serum IL-9level inpatients with systemic sclerosis significantly was increased in Japanese, and concurrentSLE patients with systemic sclerosis of serum level is obviously increased. In addition,Zhu.et al have researched that IL-3, IL-4, IL-5, IL-9and IL-13gene polymorphism andGraves’ disease in Chinese people, and the results showed that the association betweenIL-9(rs1859430, rs2069868) and Graves’ disease no significant correlation. At present there is no IL-9gene polymorphism and susceptibility between SLE are researched.Based on the above content, this study proposed to use case-control design todetect association of serum IL-9level, IL-9gene polymorphisms of SLE by ELISA andTaqMan SNP Genotyping Assay kit. The accomplishment of this study would help tofurther reveal the role of IL-9in the pathogenesis of SLE and develop new potentialtherapeutic targets.Part Ⅰ Study on the Corrlation between Serum IL-9Level andSystemic Lupus ErythematosusObjective To compare the serum IL-9levels between patients with SLE and normalcontrols, patients with and without nephritis, active and inactive SLE patients.Combined with clinical and laboratory data, the relationship among their serum levelsand SLE disease activity and organ damages were further analyzed.Methods A total of86SLE patients were recruited from Department of Rheumatologyand Immunology of Anhui Provincial Hospital and the First Affiliated Hospital of AnhuiMedical University. Diagnosis of SLE was established according to the1997revisedcriteria of American College Rheumatology.85normal controls were recruited fromteaching staff and postgraduate students of Anhui Medical University. Patients andcontrols were age-, sex-matched. The demographic and clinical data were collected byquestionnaire. Disease activity was evaluated using the SLE Disease Activity Index(SLEDAI) score. After obtaining the informed consent, blood samples from all studiedsubjects were collected. Serum IL-9levels were detected by Enzyme-linkedImmunosorbent Assay (ELISA). The data were analyzed by SPSS11.5software. All Pvalues were calculated based on two-sided tests, with a statistical significance definedas P value <0.05. Results(1) Comparisons of serum IL-9level between different groups There were significantdifferences of serum IL-9level between patients with SLE and normal controls((31.30±16.93) pg/mL vs.(40.65±17.96) pg/mL, P=0.001), patients with and withoutnephritis ((35.45±16.91) pg/mL vs.(28.01±16.36) pg/mL, P=0.041). There was nosignificant difference between active and inactive SLE patients ((31.06±16.69) pg/mLvs.(31.79±17.81) pg/mL, P=0.851).(2) Correlations between serum IL-9level and SLEDAI Correlation analysis betweenserum IL-9level and SLEDAI showed no significant association (r=0.003, P=0.978).(3) Association of serum IL-9level and clinical, laboratory data of SLE patientsSignificant association was found between serum IL-9level and oral ulcer (P=0.029)and renal involvement(P=0.0041). As for laboratory features, serum IL-9level wassignificantly associated with anti-dsDNA antibodies (P=0.037) and anti-SSB antibodies(P=0.005).Conclusions In summary, our study showed a significant difference of serum IL-9levelbetween patients with SLE and normal controls, patients with and without nephritis.However, there was no significant difference between active and inactive SLE patients.We also detected significant association of serum IL-9level with part of clinical andlaboratory features. Part Ⅱ Association Study of IL-9Gene Polymorphisms andSystemic Lupus ErythematosusObjective To compare the differences of allele and genotype frequencies about twoSNPs (rs1859430、rs2069868) of IL-9between SLE patients and normal controls, and toexplore the association of IL-9polymorphisms with susceptibility to SLE.Methods SLE patients were recruited from Department of Rheumatology andImmunology of Anhui Provincial Hospital and the First Affiliated Hospital of AnhuiMedical University. All SLE patients fulfilled the1997revised American College ofRheumatology classification criteria. Normal controls were recruited from healthyblood donors, teaching staff and postgraduate students of Anhui Medical University.The demographic and clinical data were collected by self-designed questionnaire. Afterobtaining the informed consent, blood samples from all studied subjects were collected.The genotypes of the rs1859430and rs2069868SNPs were determined by the TaqManSNP Genotyping Assay kit using an ABI7300Real-Time polymerase chain reaction(PCR) system.SPSS11.5software was used for statistical analysis. The chi-square test or Fisher’sexact test was applied to compare the distribution of allele and genotype frequenciesbetween SLE patients and normal controls. P values were calculated based on two-sidedtests, with a statistical significance defined as P value <0.05.Results(1) Association of rs1859430and SLE There is a number of562SLE patients and629normal controls were recruited. The genotype frequencies of GG、AA、AG were93.4%,0.5%,6.1%in SLE patients and94.1%,0.2%,5.7%in controls. The allele frequenciesof G, A were96.4%,3.6%in SLE patients and97.0%,3.0%in controls. There was no significant differences between SLE patients and controls about genotype (AA vs. GG:OR=0.296,95%CI0.031-2.851, P=0.537; AG vs. GG: OR=0.939,95%CI0.579-1.522,P=0.798; AA+AG vs. GG: OR=0.887,95%CI0.554-1.420, P=0.617) and allelefrequencies (A vs. G: OR=0.844,95%CI0.537-1.326, P=0.461).The allele frequencies of G, A were96.6%,3.4%and the genotype frequencies ofGG、AA、AG were93.6%,0.4%,6.0%in lupus nephritis (LN) patients. They were96.3%,3.7%,93.3%,0.6%and6.1%respectively in non-LN patients. There was nosignificant differences between LN patients and non-LN patients about genotype (AA vs.GG: OR=1.431,95%CI0.129-15.885, P=1.000; AG vs. GG: OR=1.022,95%CI0.505-2.069, P=0.951; AA+AG vs. GG: OR=1.050,95%CI0.532-2.069, P=0.889)and allele frequencies (A vs. G: OR=1.073,95%CI0.563-2.043, P=0.831).(2) Association of rs2069868and SLE There is a number of660SLE patients and648normal controls were recruited. The genotype frequencies of GG, AA, AG were73.5%,2.0%,24.5%and the allele frequencies of G, A were85.8%,14.2%in SLE patients.They were74.7%,1.4%,23.9%,86.7%and13.3%respectively in controls. There wasno significant differences between SLE patients and controls about genotype (AA vs.GG: OR=0.694,95%CI0.294-1.638, P=0.402; AG vs. GG: OR=0.959,95%CI0.744-1.236, P=0.745; AA+AG vs. GG: OR=0.939,95%CI0.733-1.203, P=0.619)and allele frequencies (A vs. G: OR=0.928,95%CI0.743-1.159, P=0.50).The allele frequencies of G, A were86.3%,13.7%and the genotype frequenciesof GG, AA, AG were74.2%,1.6%,24.2%in LN patients. They were85.5%,14.5%,73.1%,2.2%and24.7%respectively in non-LN patients. There was no significantdifferences about allele (A vs. G: OR=1.069,95%CI0.775-1.475, P=0.683) andgenotype frequencies (AA vs. GG: OR=1.340,95%CI0.407-4.413, P=0.848; AG vs.GG: OR=1.039,95%CI0.719-1.504, P=0.837; AA+AG vs. GG: OR=1.058,95%CI0.739-1.516, P=0.757) between LN patients and non-LN patients. Conclusions There wae no significant difference between SLE patients and normalcontrols regarding the SNPs of rs1859430, rs12069868with the two variants. The IL-9gene polymorphisms may not be associated with susceptibility to SLE in the Chinesepopulation. |
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