Mucosal Immunity in Primary Glomerulonephritis: II. Study of the Serum IgA Subclass Repertoire to Food and Airborne Antigens

Abstract

IgA specific for 7 food and 6 airborne antigens were sought in the serum of 30 adult patients with IgA mesangial nephropathy (IgA GN), 23 with membranous nephropathy (MGN), 20 with idiopathic nephrotic syndrome (INS), 11 with membranoproliferative GN (MPGN) and 22 healthy controls by means of an enzyme-linked immunoassay. The IgA subclass was determined using monoclonal antibodies. Increased levels of IgA specific for gliadin, bovine serum albumin (BSA), ovalbumin, lysozyme and α-lactalbumin were found in IgA GN, while increased levels of IgA to BSA, ovalbumin, lysozyme and α-lactalbumin were observed in MGN; IgA specific for α-lactalbumin were increased in INS, and MPGN patients had reduced levels of IgA to BSA and increased levels of IgA to β-lactoglobulin and α-lactalbumin. These specific IgA to food antigens were restricted to the IgAl subclass. Patients with IgA GN had significantly increased levels of IgA specific for Dermatophagoides pteronyssinus (DP) and Dactil while the MGN group showed increased levels of IgA specific for DP, feathers, Dactil and mold. INS patients had increased levels of IgA specific for DP, feathers, Dactil, mold and dog hairs, while MPGN patients had increased levels of IgA specific for feathers, Dactil, dog hairs and mold. All these specific IgA to airborne antigens were restricted to the IgA1 subclass. Patients with the four types of primary glomerulonephritis had decreased IgA specific for cat hairs which were of both the IgA1 and IgA2 subclasses. We conclude that anomalies of the IgA repertoire to environmental antigens are also encountered in primary glomerulonephritis other than IgA GN.

Histone-Reactive IgA Antibodies in Adult IgA Nephropathy and Other Primary Glomerulonephritis

“…Therefore, pathologic IgA reactivities in IgAGN do not simply result from elevated IgA levels in this particular group of patients. This view is further supported by the lack of correlation between abnormal IgA reactivities and total serum IgA levels seen in this and previous reports [16]. histones.…”

“…Most investigators have compared the levels of IgA anti bodies to a given antigen between IgAGN patients and normal controls. The results in the present study and in our previous observations [15,16] indicate, however, that certain abnormal IgA reactivities and possibly certain pathogenic mechanisms might be common to various PGN. Therefore, pathologic IgA reactivities in IgAGN do not simply result from elevated IgA levels in this particular group of patients.…”

“…Thus, we have observed that mucosal IgA antibodies are increased not only in IgAGN but also in MGN and INS [15]. We have recently also reported that increased serum IgAl reactivity to food and air-borne anti gens is found in IgAGN and other types of PGN [16].…”

“…In addition, no correlation was found between the confounding factors, namely total serum IgA, 24-hour proteinuria, serum crea tinine and creatinine clearance, and the levels of the reacti vities against total or individual histones in the four PGN groups. Assays conducted on four positive sera for each type of glomerulonephritis with reagents specific for either the IgAl or IgA2 human subclasses [16] [32], This could result either from the low sensitivity of the immunofluorescence method or from the lack of accessi bility of some histone epitopes in chromatin.…”

“…For IgA subclass antihistone antibodies a modified indirect ELISA was used [16]. Briefly, after incubation with the sera, the antigen-coated plates were washed and monoclonal antibodies spe cific for either IgAl (clone NIF2, Zymed, USA) or IgA2 [mixture of two monoclonal antibodies: clone 2E2 (Zymed, USA) and clone N 1-512 (Nordic, The Netherlands)] were added for 2 h at room temperature, followed by biotinylated affinity-isolated rabbit IgG antimouse IgG (human immunoglobulin adsorbed, Zymed, USA) and streptavidin-alkaline phosphatase (Zymed.…”