The Relationship Between TIM-1and TIM-3Polymorphism With Myasthenia Gravis Associated With Thymoma

Myasthenia gravis(MG) is a kind of autoimmune disease with dysfunction of neuromuscular junction. The main pathological mechanism is reduction of acetylcholinesterase receptor(AChR). The associated antibodys and proteins,helper T cells,cytokines,chemokines are involved in the pathogenesis of MG in which fifty percent patients have thymic lesions. One of the possible mechanisms:Thymus is the organ which induced T cells differentiation;Abnormal strcture and function of the thymus cause genes of T cell rcepters rearrangement; The thymus can not eliminate or inhibit T cell clones against autoantigens and shows the obstacles of immune tolerance to self antigens and activates autoimmune responses. In addition, immature T cells with CD4+or CD8+in thymus decrease, then mature T cells with CD4+or CD8+in thymus increase.Most of the autoimmune diseases and Allegic diseases are related with imbalance of the numbers of Thl and Th2cells. Increase of the number of Th2cells and fuctions can suppress the pathogenesis of Autoimmune disease.People have already cloned reactive Thl cells in of Ach-R in normal human. Berrih—Aknin reports that hyperplasia of the thymus can express T cell receptors which points the possible relationships with the pathogenesis.It was the first time to confirm that phenotype of T cells in thymus change in autoimmune diseases.Recent studys show that Tims family genes which express on the surface of T cells palys an important role in regulating the immune response mediated by Thl and Th2cells.In human, the number and functions of Thl and Th2cells keep in balance,which keeps a normal autoimmune state to response to the pathogens.If some factors changed, like antigenic characteristics or numbers changes,or the type of antigen-presenting cells are changes, or the cytokines changes,or some micro-enviromental factors changes,can cause different diseases[5]. TIM family genes plays an important role in regulating immune responses.It causesallergy, asthma,tolerance inhabition,autoimmune diseases,virus infection.More and more studys show that imbalance of Thl and Th2cells and cytokines which is seceted by Thl and Th2cells is related with the pathogenesis of Asthma.Genes related with the induced and differectiation of Thl and Th2cells affects the pathogenesis of Asthma through initiating the induced and differectiation or imbalance of Th1and Th2cells. The distinctive variable area structure of TIM immunoglobin is phosphatidylserine, which is expressed on the surface of apoptotic cells.Both TIM-1,TIM-3can recognize phosphatidylserine,but have different expression. This shows that TIM-1and TIM-3have different functions of regulating immune responses.Tim-1is expressed on the surface of Th2cell and regulating immune responses of Th2cells.TIM-3is expressed on the surface of Thl cell and has function of negative immune regulation of Thl. Based on the important immune regulating function on Th1and Th2cells, TIM-1and TIM-3genes have been to the susceptibility gene of asthma. Since the TIM-1gene was found, the members of this family gene has been a research focus.But there is still less research on the relationship ofTIM-1, TIM-3and MG. So we do the reach on this two aspects.In this study, we firstly investigated the expression of TIM-1and TIM-3inmyasthenia gravis patients. TIM-1gene polymorphism-1637A/G and TIM-3gene polymorphism-574G/T at promoter were genotyped by single allele-specific primer polymerase chain reaction (SASP-PCR).Objective:To evaluate the relationship between TIM-1and TIM-3single nucleotide polymorphism with myasthenia gravis associated with thymoma. Method:234patients with thymoma and (or) MG, which include58patients associated with myasthenia gravis、62patients without myasthenia, and50myasthenia gravis patients without thymoma、64healthy people as controls were investigated. TIM-1gene polymorphism-1637A/G and TIM-3gene polymorphism-574G/T were genotyped by single allele-specific primer polymerase chain reaction (SASP-PCR).Result:(1) Statistic differences in genotype frequency of-1637A/G were observed between MG(+)-thymoma and MG(-)-thymoma, MG-thymoma(-) controls (P=0.031,0.028and0.000), but not observed between MG(-)-thymoma,MG-thymoma(-) and controls (P＜0.05). Statistic differences in alleles frequency of-1637A/G were observed between MG(+)-thymoma and MG(-)-thymoma, MG-thymoma(-) controls (P=0.000,0.046and0.000), but not observed between MG(-)-thymoma,MG-thymoma(-) and controls (P<0.05).(2) Statistic differences in genotype frequency of-574G/T were observed between MG(+)-thymoma and MG(-)-thymoma, MG-thymoma(-) controls (P=0.016,0.018and0.000), but not observed between MG(-)-thymoma,MG-thymoma(-) and controls (P＜0.05). Statistic differences in alleles frequency of-574G/T were observed between MG(+)-thymoma and MG(-)-thymoma, MG-thymoma(-) controls (P=0.024,0.026and0.001), but not observed between MG(-)-thymoma&MG-thymoma(-) and controls (P＜0.05).Conclusion:1.There is polymorphism sites of the promoter region in TIM-1,-1637A/G polymorphism sitemay be associated with myasthenia gravis.2.There is polymorphism sites of the promoter region in TIM-1,-574G/T polymorphism site may be associated with myasthenia gravis.