SERIAL FUNCTIONAL AFFINITY OF AUTOANTIBODIES IN ANTIGLOMERULAR BASEMENT-MEMBRANE DISEASE

Anti-glomerular basement membrane (GBM) disease is caused by an autoan tibody directed against an epitope on the alpha 3 chain of type IV col lagen. Animal models demonstrate that the higher the affinity of such antibodies, the greater the degree of glomerular injury. Affinity matu ration (the process whereby somatic mutation followed by antigen selec tion leads to an increase in affinity of antibody) might therefore be of pathogenic significance if it occurs in human anti-GBM disease. We have examined serial samples from nine patients with anti-GBM disease and looked for evidence of changing functional affinity by measuring t he inhibition of binding produced by the mild chaotrope diethylamine ( DEA) in an anti-GBM antibody ELISA. Seven patients showed no change in the inhibition produced by DEA with time. Two patients showed an appa rent decrease with time in the inhibition produced by DEA; this appare nt increase in functional affinity proved, on further investigation, t o represent simply the loss of anti-GBM antibodies. These results may imply that affinity maturation has been completed by the time that pat ients present with anti-GBM disease. If there had been evidence for a further increase in functional affinity after this point then this mig ht have added extra urgency to the need for removal of these autoantib odies as part of treatment.