2017-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/691560Systemic lupus erythematosus (SLE) is more prevalent in Chinese Han population and is often life-threatening, yet the pathogenic cause and mechanism remain mostly unclear. It has been demonstrated that recognition of bacterial DNA by Toll-like receptor (TLR)-9 on B cells or dendritic cell could facilitate autoantibody secretion and aggravate renal disease in lupus-prone mice. However, serum DNA autoantibody levels on renal pathology and survival in murine lupus model were controversial, not mentioning that the origin of autoantibodies that contribute directly to the pathogenesis of SLE is largely unknown. Our preliminary results demonstrated that 17 kDa protein derived from commensal streptococci in the oral cavity may induce pathogenic autoantibody. We further identified it to be a RNA binding protein, which may be the target antigens responsible for the generation of pathogenic autoreactive autoantibodies in SLE patients but not in healthy donors. Those patients with positive anti-17 kDa antibody showed lower plasma haptoglobin and higher prevalence of autoimmune hemolytic anemia. Clinical serology was surveyed as several known antoantigens also have RNA binding capacities(such as 60 kDa Ro protein), but none of these antibody tilters against RNA binding protein or dsDNA were shown to correlated well with anti-17KDa levels. We propose to determine the the role of RNA binding protein in immunopathogenesis in SLE and lupus nephritis. In this project, we hypothesize that the autoantibody production in SLE could be induced by commensal bacterial infection due to the cross-reaction with RNA binding protein. Therefore, the specific aims of this project include: 1. Characterization of streptococcal bacterial proteins those are responsible for induction of pathogenic autoantibody production. 2. Investigation of the underlying mechanisms of pathogenic autoantibody production induced by the streptococcal RNA-binding protein in SLE 3. Evaluation of the role of the RNA-binding protein in the pathogenesis of lupus nephritis in a lupus-prone murine model 4. Evaluation of the clinical application of the commensal-associated antibodies in diagnosis and prognosis of SLE.systemic lupus erythematosuscommensal bacteriaRNA-binding proteinautoantibodylupus nephritis