Immunogenetic Features Of Systemic Lupus Erythematosus And Its Clinical Relevance With HLA Gene

Systemic lupus erythematosus (SLE) is a complex, chronic, autoimmune disorder that can cause severe health damage to the patients, even potentially fatal. The exact causes and mechanism of SLE are still not clear. Currently, it is widely accepted that the initiation and progression of SLE are closely associated with genetic factors, environmental inducing factors and the immunopathological changes, the genetic and immune factors play the key role the pathogenesis of SLE.In this study, the potential mechanism of SLE on the genetic and immune level, and the association between the polymorphism of HLA-DM and the clinical detection of SLE, were explored to evaluate the possibility of applying the genetic analysis in predicting susceptibility, progression and prognosis of SLE. The study mainly included several parts as followedPartⅠ. Analysis of relativity between HLA-MD gene and SLE. The HLA-DM genotypes of SLE patients and controls were determined by PCR-RFLP. 4 alleles and 6 genotypes of HLA-DMA were detected, 3 alleles and 6 genotypes for HLA-DMB. The frequency of all the HLA-DM genes in SLE patients was analyzed in order to search for the potential HLA-DM genotypes related to the SLE susceptibility. The result showed that the distribution of HLA-DMB*0101/0103 genotype in SLE and control was different, significantly higher in SLE. That suggested that HLA-DMB*0101/0103 genotype was related with the SLE susceptibility.PartⅡAssociation between HLA-DM genotype and the clinical tests of SLE, including the autoimmune antibodies of SLE patients, the activity of SLE disease and renal dysfunction. The result demonstrated that: (1) the positivity rate of anti-U1-RNP antibodies increased in SLE patients with HLA-DMB*0103 allelotypes. (2) Compared with those with HLA-DMB*0101 allelotypes, the illness state was more active in the SLE patients with HLA-DMB*0102, who suffered form renal damage more frequently. (3) For SLE patients with HLA-DMB*0101/0103 genotypes, the progression was relatively slow and stable, general condition was better. (4) Renal damage and SLE nephritis happened more frequently in the patients with HLA-DMB*0101/0102 genotypes. All these indicated that there existed certain association between HLA-DM polymorphism and generation of auto-antibodies in SLE patients, activity of SLE and renal damages. To certain degree, HLA-DM polymorphism could predict the disease activity and renal damages in the SLE patients.PartⅢThe effect of cytokine changes on SLE. The expression of IL-10mRNA、IL-18mRNA、FasmRNA in PBMC from SLE patients were detected with qRT-PCR. IFN-γ、IL-2、IL-4、IL-10 and IL-18 in patient serum were measured by means of ELISA, the association between cytokine changes and auto-antibody against ds-DNA was analyzed. The result showed that the expression of IL-10 mRNA、IL-1 mRNA 8、Fas mRNA were obviously higher in PBMC from SLE patients than control group. The concentrations of IFN-γ、IL-4、IL-10、IL-18 were also much higher in the serum of SLE patient( IL-2 lower). Compared with those of ds-DNA auto-antibody negative, the expression of IL-10mRNA、IL-18mRNA、Fas mRNA and serum concentration of IFN-γ、IL-4、IL-10、IL-18 were much higher(IL-2 lower) in the SLE Patients of ds-DNA auto-antibody positive.PartⅣSLE and apoptosis. By detecting the DNA fragmentation and the percentage of cells of sub-diploid with flow-cytometry, the apoptosis in lymphocytes from SLE patients were analyzed for further exploration of the relation between lymphocyte apoptosis and auto-antibodies. The result showed that there were more lymphocyte apoptosis in SLE patients than in control group, which seemed associated with the numders of auto-antibodies. The number of lymphocyte in apoptosis increased significantly in patients with more than 2 auto-antibodies, compared with patients with only one auto-antibody.