IgA in IgA nephropathy.

IgA in IgA Nephropathy Lorna Layward IgA nephropathy is a common glomerulonephritis of unknown pathogenesis, characterised by the presence of IgA within the glomerular mesangium. The predominant subclass of deposited IgA is known to be of the subclass IgA1 and is, at least in part, polymeric. IgA subclass measurements showed that raised serum IgA levels were restricted to the IgAl subclass, and that increased IgA levels were only observed in the systemic (not mucosal) compartment of the IgA immune system. In vitro production of IgA by peripheral blood lymphocytes was increased, with a concomitant decrease in IgG production. The response to systemic challenge with tetanus toxoid demonstrated a bias towards serum IgA1 antibody production; an enhanced circulating antigen-specific B cell response; and a positive saliva response where none was observed in controls. Serum polymeric IgA antibody production in response to systemic antigen challenge was significantly elevated in IgA nephropathy. Patients with IgA nephropathy were more likely to have an IgG subclass antibody deficiency than controls, showing dysregulation of other isotypes besides IgA. The affinity of serum IgA antibodies produced was lower than controls, while IgG affinity was normal. The production of low affinity IgA antibodies may result in the formation of nephritogenic immune complexes and explain the predominance of IgA within the glomerular mesangium. Gut permeability was normal in IgA nephropathy, and the response to mucosal antigen challenge did not differ from controls except for a higher antigen-specific in vitro B cell response. These results suggest an enhanced overlap of circulating IgA immunocompetent IgA B cells between the two sites in IgA nephropathy, regardless of the route of antigen administration. These data show abnormalities of mainly systemic IgA lending support to the hypothesis that the source of IgA overproduction is the systemic rather than the mucosal compartment of the IgA immune system.