Restriction of human IgG subclass expression in the population of auto-antibodies to glomerular basement membrane

To study the possible relationship between individual subclass expression and pathogenesis of antibody-mediated disease, we examined the immunoglobulin-G subclass of antiglomerular basement membrane (GBM) antibodies, in the sera of 20 patients with auto-antibody mediated nephritis, as well as in a limited number of kidney eluates, using a solid phase radioimmunoassay and monoclonal antibodies specific for human IgG subclasses. Only anti-GBM antibodies of the IgG1 and/or IgG4 subclass were detectable, both in the circulation and in renal eluates. Recurrence of circulating anti-GBM antibody during convalescence occurred in two patients out of 49 studied sequentially for more than 12 months. In both cases only antibodies of a single subclass were involved. The recurrence of IgG1 antibody (which can fix complement and bind macrophages) was associated with clinical manifestations of disease, whereas the reappearance of IgG4 antibody (which cannot engage amplifiers of the inflammatory response) did not appear to be harmful. Thus, in anti-GBM auto-antibody mediated nephritis, clear restriction in the subclass of IgG auto-antibody occurs, and this may be important in disease expression.