Naturally occurring interspecies and intraspecies antiimmunoglobulin antibodies

In a recent study, using the beagle dog transplantation model, we examined the effect of the administration of murine mAbs specific for dog T lymphocytes or class II MHC antigen on renal allograft survival. In a solid-phase radioimmunoassay assay (RIA), we observed that untreated dog serum contained 'naturally occurring' antimouse IgG antibodies. This observation has been extended in the present brief report to include studies in normal human laboratory volunteers and patients before and after renal transplantation. We have tested the sera for the presence of natural antibodies reactive with mouse IgG. Moreover, we asked whether the antimouse IgG antibody, when isolated from human serum by affinity chromatography, would also react with autologous, allogeneic, or xenogeneic (horse) IgG. We have also treated neat sera for the presence of heat-labile and heat stable factors that might inhibit the binding of these naturally occurring antibodies to their IgG ligands, and whether the level of the naturally occurring antimouse activity might be altered after renal transplantation with immunosuppressive regimens. In the present study, we have demonstrated that the naturally occurring human antimouse antibodies also recognize epitopes on human and horse IgG molecules. Additionally, the degree of binding of affinity chromatography-isolated antimouse antibodies is, at least in part, regulated by heat-labile and stable serum factors. There was also a marked decrease in the level of these naturally occurring antimouse IgG antibodies in the sera of patients after transplantation (but the antibodies were still routinely detectable, albeit in decreased concentrations in the assay if diluted from neat serum). This observation may, in part, explain why, although OKT3 treatment for rejection episodes has been effective, it has had limited applicability for repetitive or prolonged treatment courses, due to the low, but now detectable, level of preexisting antimouse antibodies in immunosuppressed patients.