Screening Of Systemic Lupus Erythematosus Biomarkers And Study Of Pathogenic Mechanisms

Systemic lupus erythematosus(SLE)is a typical inflammatory autoimmune disease with multi system and organ involvements.It ranges from a relatively mild disorder to rapidly progressing,affecting many body systems and most commonly affects the skin/muscles,lining of lungs,heart,nervous tissue,and kidneys with unclear etiology.It's associated with abnormalities of immune system and results from interactions among genetic,hormonal,environmental,and immunologic factors.It's considered that autoantibody production,immune complex tissue deposition and activation of complements have been implicated in the pathogenesis of SLE.SLE is diagnosed primarily on criteria relating to patient history,physical examination,and laboratory findings,and biomarkers,such as inflammatory factors,autoantibodies and cytokines are uaully used to evaluate disease activity of SLE and treatment effect.While,there are no ideal biomakers to evaluate the progress and clinical classifications of all patients due to individual variability.Therefore,we are aim to research for new serum biomarkers and explore their molecular mechanism for a better way to diagnose and treat SLE.First,we detected the expression of 20 autoimmune antibodies in SLE sera Luminex high-throughput protein detection technology and screened out several autoimmune antibodies which expressed highly and specific in SLE patients,best combined diagnosis for SLE,autoimmune antibodies which were associated with disease activity,and autoimmune antibodies which were significantly related to antinuclear antibody(ANA)and anti dsDNA antibody.Then,by clustering analysis we found that 20 autoimmune antibodies expressed in SLE sera in certain profiles and autoimmune antibodies belonging to the same antibody family were similar.And later we proved that autoimmune antibodies from the same antibody family existed in peripheral blood of SLE patients in form immune complexes.Immune complexes travelled in the vascular system to different target organs and led to the deposition and complements activition causing organ demage.We also found that autoimmune antibodies from different antibody spectrum were associated with different organ involvement.Among them,we found that deposition of anti-UlsnRNP immune complex in kidney tissues of SLE patients was correlated with serum expression level of anti-UlsnRNP,kidney pathological damage and functional damage,which indicated that anti-UlsnRNP antibodies can be used as biological indicator of kidney damage in SLE patients.Further more,we also found that the type I interferons and type I IFN induced genes played important roles in the pathogenesis of SLE,and type I interferon can be used as evaluation index of SLE disease activity,IFI27,ISG15,SIGLEC1 as biomarkers of LN.In conclusion,our study first systematically analyzed various autoimmune antibodies expression in SLE patients,screened out autoimmune antibodies for combined diagnosis of SLE and revealed that autoimmune antibodies existed in the peripheral blood and tissues of SLE in form of autoimmune complexes,associated with specific organ damage.Then we put forward that anti UlsnRNP antibodies can be used as a clinical biomarker to evaluate kidney damage of SLE patients,which enriched biomarkers to help diagnose and treat SLE and provided clues for better understanding of the pathogenesis of SLE.And IFN and IFN induced genes played important roles in the process of SLE,which can be used as biomarkers of SLE.