BACKGROUND: The presence and the pathogenetic role of circulating IgA reacting with neutrophil cytoplasmic antigens (IgA-ANCA) in patients with Henoch-Schönlein purpura (HSP) is still debated. This study was aimed to investigate some characteristics of serum IgA and macromolecular IgA in HSP patients, focusing on IgA-ANCA. METHODS: Eighty-seven HSP patients with biopsy proved renal involvement (51 adults and 36 children) enrolled in a multicentre study of the Italian Group of Immunopathology were investigated. RESULTS: Significantly high levels of IgA immune complexes were found in both adults (P < 0.05) and children (P < 0.01), while the binding of IgA to jacalin, was significantly low in children with HSP (P < 0.01) only. Two series of ELISA were done for IgA-ANCA, in two different laboratories. Increased binding to PMN crude extracts (P < 0.01) without any modification in IgA binding to proteinase 3 was found by either specific ELISA. Conversely, the binding of IgA to myeloperoxidase (MPO) was found to be significantly (P < 0.05) increased with positive values in 25% of patients by one assay only. Three of four sera with positive IgA-MPO ANCA exhibited binding in Western-blot studies with the MPO preparation used in ELISA to a 28-kDa species. D-galactose and N-acetyl-glucosamine decreased the binding of serum IgA to MPO more in HSP than in controls (P < 0.05). CONCLUSIONS: The conflicting reports on IgA-ANCA may reflect some atypical characteristics of the reaction which can be detected only by some ELISAs. We suggest that not an antigen-antibody reaction but a lectinic interaction due to abnormal composition of IgA carbohydrate side chains may account for the IgA-ANCA reaction in patients with HSP nephritis.
BACKGROUND: The presence and the pathogenetic role of circulating IgA reacting with neutrophil cytoplasmic antigens (IgA-ANCA) in patients with Henoch-Schönlein purpura (HSP) is still debated. This study was aimed to investigate some characteristics of serum IgA and macromolecular IgA in HSP patients, focusing on IgA-ANCA. METHODS: Eighty-seven HSP patients with biopsy proved renal involvement (51 adults and 36 children) enrolled in a multicentre study of the Italian Group of Immunopathology were investigated. RESULTS: Significantly high levels of IgA immune complexes were found in both adults (P < 0.05) and children (P < 0.01), while the binding of IgA to jacalin, was significantly low in children with HSP (P < 0.01) only. Two series of ELISA were done for IgA-ANCA, in two different laboratories. Increased binding to PMN crude extracts (P < 0.01) without any modification in IgA binding to proteinase 3 was found by either specific ELISA. Conversely, the binding of IgA to myeloperoxidase (MPO) was found to be significantly (P < 0.05) increased with positive values in 25% of patients by one assay only. Three of four sera with positive IgA-MPO ANCA exhibited binding in Western-blot studies with the MPO preparation used in ELISA to a 28-kDa species. D-galactose and N-acetyl-glucosamine decreased the binding of serum IgA to MPO more in HSP than in controls (P < 0.05). CONCLUSIONS: The conflicting reports on IgA-ANCA may reflect some atypical characteristics of the reaction which can be detected only by some ELISAs. We suggest that not an antigen-antibody reaction but a lectinic interaction due to abnormal composition of IgA carbohydrate side chains may account for the IgA-ANCA reaction in patients with HSP nephritis.