Properties of circulating IgA molecules in Henoch-Schonlein purpura nephritis with focus on neutrophil cytoplasmic antigen IgA binding (IgA-ANCA): new insight into a debated issue

Background: The presence and the pathogenetic role ofcirculating IgA reacting with neutrophil cytoplasmic antigens (IgA-ANCA) inpatients with Henoch-Schonlein purpura (HSP) is still debated. This studywas aimed to investigate some characteristics of serum IgA andmacromolecular IgA in HSP patients, focusing on IgA-ANCA.Methods: Eighty-seven HSP patients with biopsy provedrenal involvement (51 adults and 36 children) enrolled in a multicentrestudy of the Italian Group of Immunopathology were investigated.Results: Significantly high levels of IgA immunecomplexes were found in both adults (P <0.05) and children (P<0.01), while the binding of IgA to jacalin, was significantly lowin children with HSP (P <0.01) only. Two series of ELISA were donefor IgA-ANCA, in two different laboratories. Increased binding to PMN crudeextracts (P <0.01) without any modification in IgA binding toproteinase 3 was found by either specific ELISA. Conversely, the binding ofIgA to myeloperoxidase (MPO) was found to be significantly (P <0.05)increased with positive values in 25% of patients by one assay only. Threeof four sera with positive IgA-MPO ANCA exhibited binding in Western-blotstudies with the MPO preparation used in ELISA to a 28-kDa species.D-galactose and N-acetyl-glucosamine decreased the binding of serum IgA toMPO more in HSP than in controls (P <0.05).Conclusions: The conflicting reports on IgA-ANCA mayreflect some atypical characteristics of the reaction which can be detectedonly by some ELISAs. We suggest that not an antigen-antibody reaction but alectinic interaction due to abnormal composition of IgA carbohydrate sidechains may account for the IgA-ANCA reaction in patients with HSPnephritis.