Epibodies in autoimmunity: Antisera against autoantibodies to the renal glomerular basement membrane react with idiotypes as well as with autoantigens

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Abstract
The results reported here show that we have experimentally produced xenogeneic anti-idiotypic antibodies to rat autoantibodies specific for the renal GBM and one of its components, laminin. Cross-reactive idiotypes have been detected by anti-idiotypic antibodies (anti-Id) on autoantibodies to the GBM (anti-GBM) from rats of different strains, confirming the results obtained in other autoantibody systems. During the course of studies aimed at determining whether anti-Id were directed to the paratope of anti-GBM antibodies, we have observed the presence of anti-GBM (and anti-laminin) antibodies in rabbit sera with anti-Id. Affinity chromatography experiments suggest that anti-GBM reactions detected with our anti-Id sera may be caused by a heterogeneous combination of anti-Id. Thus, Ab2 alpha (and/or Ab2 gamma, all reacting with Ab1), Ab2 epsilon (epibodies, that bind to both Ab1 and GBM) and Ab3 (similar to Ab1 and therefore, reacting with GBM) may be present in our anti-Id sera. It has been suggested that antibodies displaying epibody properties may be involved in the mutual regulation of autoreactive clones and represent an important component of the autoimmune process.