| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 90 === ABSTRACT
Systemic lupus erythematosus ( SLE ) is characterized by the existence of a heterogeneous group of autoantibodies. These autoantibodies can bind to autoantigens to form immune complexes. These immune complexes might circulate to deposit in kidney glomerula, finally can activate complement reaction and then result in kidney inflammation and damage. Uremia caused by glomeruonephritis is the most important factor for the mortality of both human and mice lupus. More and more recent studies have demonstrated that in addition to the deposition of immune complexes in kidney, certain autoantibodies could circulate and bind to kidney autoantigens directly and then destroy the normal renal function. Mesangial cell is one of the most important cell type in glomerula, it plays many significantly physical roles. The aim of our project is to study if there is any autoantigen expressed by mesangial cells of lupus animal model NZB/WF1 mice that could be targeted by autoantibodies directly. First, we use Western blotting and ELISA to assay if there is any autoantigen in mesangial cell lysate could be recognized by autoantibodies in sera of lupus mice with disease onset. Second, according to the studies of other research groups, it is focused that α-actinin is also an important autoantigen candidate expressed by lupus mice mesangial cells. We analyzed the protein by technique of Western blotting and ELISA to assay the relationship between autoantibodies andα-actinin . Then we used T cell proliferation assay to detect if there is any α-actinin-specific T cell in BWF1 mice. We have found that there was indeed one significant autoantigen expressed by mesangial cell in lupus NZB/WF1 mice could be targeted by autoantibodies. And the result of protein sequencing showed that the autoantigen is zyxin protein. We also found the more severe the mice was, the higher reaction betweenα-actinin and autoantibodies of lupus mice sera could be seen. Finally we found that there is a group of autoreactive T cells against α-actinin existing in lupus NZB/WF1 mice. According to all the data above, it is suggested that not only the deposition of immune complexes could result in the kidney damage, the autoantigens expressed by mesangial cells attacked directly by autoantibodies might also play an important role in the pathogenesis of renal damage.
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