Anti-podocyte Antibody And Primary Membranous Nephropothy

Objective: In the dectection membrane nephropothy patient blood theanti-podocyte membrane protein immune body, studies the role ofanti-podocyte membrane protein body in primary membrane nephropothypathogensis, find out a marker of diagnose, and monitor the course ofpatients with IMN. Background: Membranous nephropathy is a commoncause of the nephrotic syndrome in adults, with glomerular subepithelialimmune complex deposition, basement membrane diffuse thickening. Themembranous nephropathy incidence accounts for about9.9%~13.5%of theprimary glomerular disease. About one-third patients can be spontaneousremission, but still have40%of the MN-patients in the10years into theend-stage renal disease(ESRD). Now majority scholars think that thepathogenesis of IMN for immune complex mechanism, immune complexdeposition in the capillary wall, activated the complement. Complementactivation leads to formation C5b-9on podocyte, and results in podocyteinjury, the structure and function of podocyte demage, appear apoptosis,necrosis and defect, the barrier function disappear, produce the proteinuria. Inrecent years, foreign scholars found that an antibodies target antigen agaginsthuman podocytes, identified as a major target antigen involved in idiopathicmembranous nephropathy in adults. In1994, SatioA studied of MN in a ratmodel(Heymann's nephritis)established that the subepithelial immunedeposits; megalin, with circulating anti-megalin antibodies are formed in situ.However, megalin is not expressed on human podocytes and is not the targetantigen in human disease. In2002, Debiecfound that neutral endopeptidase(NEP)is identified as the responsible antigen in a infant membranousnephrpathy with alloimmune antenatal. In2009, Beck, study found that a70%positivity rate in a cohort of American idiopathic MN patients, the M-type phospholipase A2receptor(PLA2R)was identified as the major targetpodocyte antigen involved in adult autoimmune idiopathic membranousnephropathy. Detection of anti-PLA2R antibodies in IMN is a very sensitivemarker. And studies have found that the antibodies will play a important rolein guiding treatment of IMN. Importantly, decrease of anti-PLA2Rautoantibody levels lead to the decline of proteinuria and, a relapse ofproteinuria, the reemergence of the autoantibody in the circulation causedrecurrence of disease, may help to monitor disease activity and guide specificintervention in patients with IMN by assessment of circulating anti-PLA2Rantibodies. In2010, Prunotto used a combined proteomic approach to identifyspecific antibodies against podocyte proteins in both serum and glomeruli ofpatients with membranous nephropathy (MN). They detected specificanti–aldose reductase (AR) and anti–manganese superoxide dismutase (SOD2)IgG4in sera of patients with MN. But there are still a third of the patients donot know what is the antigen. The prevalence of autoantibodies againstpodocytes is unknown among Chinese patients with MN. We aim to prove thetheory, using an indirect immunofluorescence method, by serologicalexamination of membranous nephropathy, for look for method of non-invasivediagonsis, to guide clinical treatment, observe the prognosis.Method: IMN serum:sixty patients diagnosed as primary MN by renalbiopsy from Marth,2010to December,2011at the second affiliated hospitalof Hebei Medical University were involved in this study. Excluded secondaryMN, including hepatitis-GN, LN, tumor-MN etc, and did not useglucocorticoid and immunosuppressant. Fixty four cases clinical24h urineprotein quantitative>3.5g, sixty patients with normal serum creatinine,GFR>90ml/min. fixty four IgA nephropathy patient were involved in thisstudy. Excluded Systemic lupus erythematosus (SLE), allergic purpura,cirrhosis, psoriasis, and did not use glucocorticoid and immunosuppressant.Clinical24h urine protein>3.5g. patients with normal serum creatinineare in range, GFR>90ml/min.Secondary MN serum: fixteen patientsdiagnosed as Ⅴ type with lupus nephritis by renal biopsy from Marth,2010to December,2011at the second affiliated hospital of Hebei Medical Universitywere involved in this study,and did not use glucocorticoid andimmunosuppressant. Clinical24h urine protein>3.5g. patients with normalserum creatinine, GFR>90ml/min.seventeen patients diagnosed as hepatitisB (HBV)-associated MN by renal biopsy from Marth,2010to December,2011at the second affiliated hospital of Hebei Medical University wereinvolved in this study, and did not use glucocorticoid and immunosuppressant.Clinical24h urine protein>3.5g. patients with normal serum creatinine,GFR>90ml/min.fixty healthy controls. Preparation from human kidneytissues frozen section, were adding IMN patients serum, IgAN patients serum,normal serum, Ⅴ type with lupus nephritis serum, and hepatitis B–associatedMN serum.(the original serum liquid not dilute) Fluorescence microscopeeach change,and calculation of postive in MN.The kidney tissues frozensection with adding IMN patients serum, further use immunohistochemicalmethod observation and IgG subtype with immune deposits and use computerimage analysis system.Results: In healthy controls and other s glomerular disease and secondaryMN, there are not IgG in the glomerular capillary wall deposition. IMNpatients serum group appeared fine granular IgG in the glomerular capillarywall deposition.60cases immunofluorescence positive18cases, the detectionrate30%.17patients of54cases of NS are immunofluorescence positive,thedetection rate31.5%. immunohistochemical method showed that IMNappeared to be characterized by glomerular capillary wall deposits ofpredominantly IgG4, a small amount IgG1and IgG3,not IgG2deposits.Conclusion:podocyte antibody is positive in IMN patient the blood, isthe main reason of IMN pathogensis.