Clinical Significance Of Autoantibodies In Assessment Of Idiopatic Membranous Nephropaty

Idiopathic membranous nephropathy(IMN)is the most common cause of nephrotic syndrome in adults,accounting for about 30%of all types of renal biopsy.In recent years,the proportion of IMN in primary glomerular diseases has the trend continues to rise.Adult patients with IMN are detected anti-M-type phospholipase A2 receptor(PLA2R)antibodies in the serum,and the M-type receptor express in human podocytes in patients with membranous nephropathy(MN),but the patients with secondary or other glomerular diseases shows less appearance of anti-PLA2R antibodies in serum,which indicates PLA2R may be pathogenic target antigen of IMN in adults.Anti-PLA2R antibody may be an important biomarker for the diagnosis of IMN.Podocyte is an important part of glomerular filtration barrier.The existing views are generally believed that circulating antibody and inherent antigen of podocyte leading to in situ formation of immune complexes deposition is the initiating pathogenesis of IMN.In 2009,Beck et al first found PLA2R for IMN specificity target antigens on the cell membrane of podocyte in an article published in the journal of《New England Journal of Medicine》.The study found that 70%anti-PLA2R are positive in IMN patients serum,and combined with PLA2R specifically on podocyte to form granular immune complex,while the secondary glomerular disease are rarely detected,which means anti-PLA2R is unique to IMN antibodies.Recent studies have also found that aldose reductase(AR)and superoxide dismutase(SOD2)is also an antigenic component that causes the onset of human IMN.In 2010,Marco Prunotto et al found specific antibodies for podocyte antigen AR and SOD2 in serum and kidney tissue of patients with membranous nephropathy by proteomics methods,both can be identified by specific circulating antibodies,also can be detected in glomerular subcutaneous immune deposits.It is speculated that SOD2 may be involved in the pathogenesis of IMN as podocyte pathogenic antigen.At present,the time,the way and the timing of the application of immunosuppressive agents in the clinical treatment of membranous nephropathy are still controversial.How to make immunosuppressive drugs under the premise of minimizing the adverse effects to get the maximum efficacy is still a hot issue.Clinically we recommended the preferred treatment regimen of hormone combined with cyclophosphamide,and the alternative to low dose of hormone combined with tacrolimus or cyclosporine A.To clarify clinical efficacy,side effects and long-term prognosis of different treatment options for patients with idiopathic membranous nephropathy can help clinicians choose the appropriate treatment according to the different circumstances of patients.Objective:To explore the relationship between the dynamic change of phospholipase A2 receptor(PLA2R),aldose reductase(AR)and superoxide dismutase 2(SOD2)antibody level in idiopathic membranous nephropathy(IMN)patients’ serum and their conditions.Comparing the efficacy of cyclical CTX/steroids with tacrolimus(TAC)/steroids to the autoantibodies titers in patients with IMN.Methods:The study included 56 IMN patients(Qianfoshan hospital,Shandong,China),whose diagnoses were supported by presenting with nephrotic syndrome and renal biopsy features of IMN.All the serums were collected for at baseline and at 1,3,6,9 and 12 months after start of therapy.Samples were tested by ELISA of anti-PLA2R,anti-AR and anti-SOD antibodies,also including urine protein quantitation and other blood biochemical indexes.Results:Anti-PLA2R antibody positivity is 70.59%in patients at baseline.After 5 months of treatment,the quantitation of urine protein has decreased as the decreasing PLA2R antibody level,whereas the increasing serum albumin.This analysis could not find any statistical difference(p>0.05)between CTX/steroids(n=36)and TAC/steroids(n=20).Anti-AR and anti-SOD antibodies positivities have no difference with normal people,also no correlation with any blood biochemical indexes.Conclusion:1.Anti-PLA2R antibody is a specific autoantibodies of IMN which is closely related to the severity of disease,instead of anti-AR and anti-SOD antibodies;2.There are no difference in the two immunosuppressive treatments for remission of IMN.