CHARGE-DISTRIBUTION OF IGA-LAMBDA IN IGA NEPHROPATHY

The finding that eluted mesangial IgA and serum IgA from patients with IgA nephropathy had a restricted anionic charge contrasting with norm al serum IgA prompted us to study the charge of the kappa and lambda s ubclasses of IgA. Serum IgA from 11 patients with IgA nephropathy and 11 controls was purified by affinity chromatography by binding to jaca lin. The charges of IgA were studied by a novel method. The spectrotyp e of total IgA was first studied by isoelectric focusing and immunoblo tting. IgA lambda and IgA kappa was further analyzed by reacting with specific monoclonal antibodies. The amount of IgA with different pIs w as analyzed by computerized densitometry. The anionic:cationic (A:C) r atio of IgA using pI 5.6 as the dividing point was greater in patients (at clinical quiescence and during exacerbation) than in controls (1. 67+/-0.31 versus 1.36+/-0.27, p<0.025). IgA lambda in both groups was anionic (A:C ratio 2.22+/-0.77 versus 2.36+/-0.36) and IgA lambda was cationic (A:C ratio 1.15+/-0.36 versus 1.04+/-0.39) but no difference in the A:C ratio was demonstrated. The increased A:C ratio in total Ig A in patients was due to raised serum IgA lambda (kappa/lambda ratio 1 .11+/-0.14 in patients and 1.51+/-0.16 in controls, p<0.01). We had pr eviously shown a predominant mesangial deposition of IgA lambda in IgA nephropathy. Animal experiments have revealed the preferential mesang ial deposition of immune complexes is related to their anionic charges . Our data of raised anionic IgA lambda in IgA nephropathy may be impo rtant in determining its selective mesangial binding that could contri bute to the immunopathogenesis.