The pathogenic role of immunoglobulin A polymers in immunoglobulin A nephropathy.
Circumstantial evidence that pIgA has a key role in glomerular injury of IgAN is now strong. Although the answers to the questions posed in this review are necessarily incomplete, they do indicate that (1) pIgA is a major component of mesangial IgA. (2) circulating pIgA is increased and this pIgA is particularly enhanced during acute hematuric relapses of IgAN. As well as true J-chain-positive pIgA, other macromolecular IgA species may circulate, including CIC, rheumatoid factors and complexes with fibronectin. (3) pIgA appears not to be derived from the mucosal lamina propria and may originate in the marrow and/or tonsil which may be unduly stimulated as a result of impaired oral tolerance. (4) Abnormalities of IgA production control are several, including genetic and cellular influences. Little is yet known about abnormalities specific for pIgA, although antigen-driven pIgA responses appear exaggerated and prolonged. In addition, pIgA enhancement may be due to activation of polyclonal antigen-independent antibody production of low affinity. (5) There is some evidence that pIgA has an enhanced capacity to bind to mesangial cells and induce injury compared to mIgA. (6) As yet, it is unclear whether pIgA has particular effects on mesangial cell activity and the induction of progressive injury. While steady progress continues in the understanding of the role of pIgA in the immunopathogenesis of IgAN, the design of therapeutic strategies based on such understanding still remains a considerable way off.
Harper
S J
SJ
Feehally
J
J
D005920:Glomerular Mesangium / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D007144:Immunoglobulin J-Chains / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008954:Models, Biological; D011108:Polymers / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D011108:Polymers; D012333:RNA, Messenger; C034639:polymeric IgA