The Role Of Aberrant N-glycosylation Of IgG4 Anti-PLA2R Antibody In The Pathogenesis Of Idiopathic Membranous

Idiopathic membranous nephropathy is a common disease in nephrology,it is an important pathological patterns in nephrotic syndrome.In recent years,the population of patients with idiopathic membranous nephropathy has gradually increased.In some areas of China,it has become the primary cause of adult glomerular disease.The prognosis of idiopathic membranous nephropathy patients varies greatly,some patients can spontaneous remissions without any treatments,meanwhile some patients eventually progress to end-stage renal disease after treatment with glucocorticoid,alkylating agents or calcineurin inhibitors.The pathogenesis of idiopathic membranous nephropathy is ambiguous up to now.Nowadays it was widely accepted that phosoholipase A2 receptor on podocyte membrane is the main antigenic site in the pathogenic process of IMN,which may be recognized by the immune system and promote the production of the anti-PLA2R antibody.Anti-PLA2R antibody recognized PLA2R on podocyte membrane and form immune complexes,which deposited under glomerular epithelium.It is considered that this is the key step in the pathogenic processing of IMN.However,it remains unclear how immune complexes damage kidney tissue after its deposition in the glomerular capillary loop.Some patients suffer severe proteinuria while the level of anti-PLA2R antibody is low.Besides,some patients with other kidney disease such as minimal change nephropathy and focal segmental glomerular sclerosis also have anti-PLA2R antibody.These suggest that the structure of the anti-PLA2R antibody also play an important part in the pathogenetic process of IMN.C3 was found in more than 70%patients’rephridial tissue,which suggests that complement is involved in the pathogenetic process of IMN.While the anti-PLA2R antibody belongs to the IgG4 type antibody which cannot activate the classical pathway of complement activation.Besides,C1q can be barely found in the renal tissue of IMN patients while more than 90%IMN patients’ renal tissue have C4d deposition.C4d is one of the product of mannan-binding lectin(MBL)pathway in complement activation.These suggests that anti-PLA2R antibody may damage renal tissue by activating the MBL pathway of complement activation.MBL can activate complement system by recognizing N-glycosylation.IgG with aberrant N-glycosylation is able to activate the MBL pathway of complement.We hypothesized that anti-PLA2R antibody with aberrant N-glycosylation activating the MBL pathway and damage the renal tissue.To explore the relationship of the aberrant of the anti-PLA2R antibody and the severity of illness,we collected blood sample from 57 patients with IMN and 62 patients with other types of nephropathy.Patients’clinical data was enrolled and their anti-PLA2R antibody was detected by ELISA.Then we detected the level of the antibody with aberrant N-glycosylation by ELISA.Compared different groups with the level of aberrant N-glycosylation showed that anti-PLA2R antibody in IMN has higher level of aberrant N-glycosylation.Besides,the level of aberrant N-glycosylation connected with systolic pressure and cholesterol level.