Macromolecular IgA and abnormal IgA reactivity in sera from children with IgA nephropathy. Italian Collaborative...

This multicenter study investigated the characteristics of circulating IgA molecules in 77 children: 42 had primary IgA nephropathy (IgAN), 20 were non-IgA glomerulonephritides (CGN) and 15 had urological problems (U). Fifteen assays were employed including the detection of macromolecular IgA [IgA immune complexes (IgAIC) by the conglutinin (K) assay, heavy molecular weight IgA in 2.5% polyethylene glycol (PEG), mixed IgA/IgGIC (Jacalin assay), IgA-Fibronectin (IgA-F) aggregates]IgA antibodies to alimentary antigens (gliadin, glycgli, glutein, ovalbumin, bovine serum albumin) and IgA binding to mesangial antigens (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine). Total IgA and IgA reacting with jacalin, supposed to bear an altered galactosylation, were measured as well. Mean levels of each kind of macromolecular IgA were significantly increased in children with IgAN in comparison to U disease (K-IgAIC p < 0.05, PEG-IgAIC p < 0.01, IgA/IgGIC p < 0.004, IgA-F aggregates p < 0.0003). However, IgA-F were the only macromolecular IgA significantly higher in IgAN than in CGN (p < 0.0005). IgA-F aggregates did not correlate with any urinary sign of activity, while K-IgAIC data were significantly related with microscopic hematuria (p < 0.05) and past history of gross hematuria (p < 0.02). Children with IgAN had mean levels of IgA reacting with the lectinic fractions of gliadin significantly higher than CGN (p < 0.01) and U groups (p < 0.003). IgAN displayed an enhanced production of IgA reacting with mesangial matrix components vs CGN (p < 0.03) and U (p < 0.0003) groups and showed altered interactions with positively charged molecules (poly-L-Lysine, p < 0.01) and carbohydrate residues (jacalin p < 0.05). In IgAN there is an increased circulation of altered IgA favouring the formation of macromolecular IgA, including true IgAIC or IgA aggregated by carbohydrate interactions. The affinity for the mesangial matrix glycoproteins and for the mesangial area electrical charge might further enhance the trapping and deposition of the immune material containing IgA. IgA-F aggregates seem to be a marker of this event, while complement binding molecules in IgAIC correspond to the hematuric manifestation of the nephritogenic process.