| Abstract: | Summary: This review seeks to highlight those aspects of ongoing research with animal models that may facilitate development of effective and perhaps specific therapy of IgAN. Oral immunization is typically accompanied by a predominantly Th2 response; defects in the evolution of this typical response, instigated by cyclophosphamide and/or oestradiol, elicit IgAN in mice. The Th2 cytokines that predominate in orally immunized mice, and in patients with IgAN, promote abnormally glycosylated IgA, similar to the IgA in patients. Immune complexes prepared with IgA antibody bearing altered glycosyl residues show enhanced rates of glomerular uptake and altered rates of clearance from the circulation. When immune responses to infectious pathogens are localized to sites remote from a new infection with a serologically related organism, ‘misdirected’ responses permit pathogen replication and antigen production concomitant with strong host antibody responses. The resultant immune complexes elicit IgAN in mice. Similar ‘misdirected’ immune responses may arise in J chain-deficient subjects. Improved pharmacologic control of B cell trafficking and/or function could rectify these defects. Correction of deficiency in clearance of IgA immune complexes could benefit patients with secondary IgAN. Finally, manipulation of glomerular haemodynamics and/or production or response to intraglomerular cytokines and growth factors might ameliorate disease or forestall progression to glomerulosclerosis. Animal models have served as a conceptual springboard for a wide variety of clinical investigations, and in turn clinical information has guided the design and goal of experimental investigation. Hopefully, this synergy can continue, ultimately resulting in effective and specific therapy. |
