HLA-SPECIFIC ANTIBODIES IN HIGHLY SENSITIZED PATIENTS CAN CAUSE A POSITIVE CROSS-MATCH AGAINST PIG LYMPHOCYTES

Background, The presence of IgG HLA-specific antibodies in the serum o f patients awaiting transplantation indicates T- and B-cell priming an d would result in acute rejection of a poorly matched human allograft. Recent advances in xenotransplantation, with the amelioration of hype racute rejection using transgenic pig kidneys, may benefit such patien ts, However, accelerated cellular rejection might result from the prim ed T-cell recognition of antigenic epitopes shared between pig and hum an MHC molecules, Methods. We have compared the reactivity of IgG anti bodies from 8 nonsensitized (NS) and 13 highly sensitized (HS) patient s with human and pig lymphocytes by flow cytometry. Xenoreactive natur al antibodies (XNA) were absorbed with pig red blood cells, and HLA cl ass I-specific antibodies were further absorbed with pooled human plat elets, Results. Before XNA absorption, 20 of the 21 patients had a pos itive IgG crossmatch with pig lymphocytes, and there was no difference between NS and HS patients, In contrast, after XNA absorption, none o f the 8 NS patients were positive, compared with 9 of the 13 HS patien ts (mean of the median channel fluorescence values of 7,7 and 86,5, re spectively; P=<0,001), For XNA-absorbed IIS patient sera, 20 of 30 (67 %) pig lymphocyte crossmatch combinations were positive, with a mean m edian channel fluorescence value of 125 (range 31 to 294) compared wit h 9.8 (range 7 to 13) for the 10 crossmatch-nepative combinations. pla telet absorption resulted in a concomitant reduction in antibody bindi ng to pig lymphocytes in three of six NS patient sera, indicating that HLA class I-specific antibodies are responsible, at least in part, fo r the positive crossmatch. Conclusion. These results suggest that some IgG: HLA-specific antibodies can bind to pig lymphocytes, analogous t o a positive crossmatch with allogeneic donors.