ANALYSIS OF CHARGE-DISTRIBUTION OF LAMBDA-IGA AND KAPPA-IGA IN IGA NEPHROPATHY BY FOCUSED ANTIGEN CAPTURE IMMUNOASSAY

The finding that eluted mesangial IgA and serum IgA from patients with IgA nephropathy (IgAN) had a restricted anionic charge contrasting wi th normal serum IgA prompted us to examine the charge of kappa- and la mbda-subclasses of IgA. Previous studies are not totally satisfactory because either total IgA without further dividing into subclass or onl y kappa- and lambda-IgA(1) was examined. A new approach is described t o study the electrostatic property of total IgA and its light chain su bclasses. The new focused antigen capture immunoassay (FACIA) allows u s to separate the immunoglobulins by isoelectric point, then to captur e by the heavy chain class and finally to visualize according to the l ight chain class. This method works well with whole blood or serum wit hout the need of prior purification by affinity chromatography. The se rum total IgA and lambda-IgA levels in patients with IgAN were signifi cantly higher than that of healthy controls. Elevated lambda-IgA level s in patients with IgAN resulted in reduced kappa/lambda ratio of tota l IgA. Similar to our previous findings in IgA(1) with O-linked oligos accharide side chain, lambda-IgA from patients with IgAN or health con trols is highly anionic whereas kappa-IgA is relatively cationic. The higher anionic/cationic ratio observed in total IgA from patients comp ared with controls was due to the higher concentration of lambda-IgA f rom the former group. Raised anionic lambda-IgA in IgAN may be contrib utory to the immunopathogenesis through its selective mesangial bindin g.