Preliminary Study Of The Relationship Between Eight Common Allergenic Foods And The Pathogenesis Of Idiopathic Membranous Nephropathy

Background M-type phospholipase A2 receptor 1(PLA2R1)and thrombospondin type-1 domain-containing 7A(THSD7A)are recognized as the two major pathogenic antigens in idiopathic membranous nephropathy(IMN).However,neither antibody to PLA2R1 nor antibody to THSD7A can be detected in about 20%of patients with IMN.According to the study of Debiec et al,immunization against cationic bovine serum albumin(BSA)in early-childhood IMN points out a possible role for food antigens in IMN.Objective To explore the possible role of 8 allergenic foods(wheat,peanut,milk,egg,soybean,shrimp,fish and hazelnut)in the pathogenensis of IMN and to evaluate their relationship with PLA2R1 in food antigen deposition in IMN.Methods We used liquid nitrogen grounding method and acetone extraction to extract food protein antigen.And ELISA indirect method was used to test and compare the serum level of specific IgG,IgA and IgE against food protein in patients with IMN(n=40),patients with IgA nephropathy(IgAN,n=15),patients with other glomerular nephritis(n= 18)and healthy individuals(n=40).We used an indirect immunofluorescence test(IIFT)to detect the deposition of eight allergenic food specific antigens in renal glomeruli from patients with IMN(n=60),patients with IgA nephropathy(IgAN,n=42),patients with minimal change disease(MCD,n=32)and patients with other forms of glomerular nephritis(n=45,including 7 lupus MN).We compared the colocalization of food antigen and IgG as well as the colocalization of PLA2R1 and IgG in patients with IMN by double-colour immunofluorescence staining combined with confocal laser scanning microscopy(CLSM).Results 1.Serum level of specific IgG against peanut protein in IMN was significantly lower than that in other glomerular nephritis controls and healthy controls(P<0.05);Serum level of specific IgG against protein of wheat,soybean or egg in IMN was significantly lower than that in healthy controls(P<0.01);Serum level of specific IgG against shrimp protein in IMN was significantly lower than that in other glomerular nephritis controls(P<0.05);There was no statistical differences in serum level of specific IgG against protein of milk or fish between IMN and each other groups(P>0.05);Serum level of specific IgG against protein of peanut,soybean,milk or shrimp in IgAN was significantly lower than that in other glomerular nephritis controls and healthy controls(P<0.05);There was no statistical differences in serum level of specific IgG against protein of wheat,egg or fish between IgAN and each other groups(P>0.05);There was no statistical differences in serum level of specific IgG against protein of wheat,peanut,bean,egg,milk,shrimp or fish between IMN group and IgAN group,and between other glomerular nephritis controls and healthy controls(P>0.05);There was no detectable specific IgG against hazelnut protein in the serum of each groups.2.There was no statistical differences in serum levels of specific IgA against protein of each food(wheat,peanut,milk,egg,soybean,shrimp and fish)in each groups(P>0.05);There was no detectable specific IgA against hazelnut protein in the serum of each groups.3.There was no detectable food specific IgE in the serum of each groups.4.Glomerular deposition of food antigens found in 66.67%(40/60)of patients with IMN and in all(5/5)patients with lupus MN;none of the patients with other kidney diseases showed glomerular deposits.5.Positive PLA2R1 staining in 82.93%(34/41)of patients with IMN and in all(5/5)patients with lupus MN;food antigens were detected in 91.17%(31/34)of patients with IMN simultaneously with positive PLA2R1 staining in the glomeruli.6.Similar to the colocalization of PLA2R1 and IgG,food antigens colocalized with IgG along the glomerular capillary walls in IMN.Conclusions Food antigens or certain components of food may play a role in the pathogenesis and progression of IMN.