Humoral immunity in renal transplantation Detection of cytotoxic antibodies to lymphocyte antigens other than HLA-A,B,C and Ia-like antigens in patients with vascular graft rejection.

By using a Fab2 fragment blocking assay with cultured human B lymphoid cells and peripheral lymphocytes as targets, cytotoxic antibodies to Ia-like antigens, to HLA-A,B,C antigens, and to lymphocyte structures other than these two types of histocompatibility antigens were identified in serial post-transplant sera from 18 renal allograft recipients. Multiple combinations of these three types of antibodies were seen in 78% of the sera. A higher reactivity as well as higher titers of antibodies were found in patients with graft failure from rejection. The occurrence of anti HLA-A,B,C or anti Ia-like antibodies did not show any relationship to graft outcome. However, cytotoxic antibodies to other antigens (referred to as non-HLA antibodies) were detected in five of the six patients with graft failure and in only one patient with graft survival. In this latter patient, non-HLA antibodies occurred with a chronic rejection episode and were no longer detectable when the rejection ceased. This study shows that the Fab2 fragment blocking assay is a useful method to identify antibodies to multiple specificities in sera from kidney graft recipients, and suggests that non-HLA cytotoxic antibodies may be associated with graft rejection.