THE ASSOCIATION OF LYMPHOCYTOTOXIC ANTIBODIES WITH CORNEAL ALLOGRAFT-REJECTION IN HIGH-RISK PATIENTS

The Collaborative Corneal Transplantation Studies are a pair of multic enter prospective clinical trials evaluating the effectiveness of hist ocompatibility matching in high risk keratoplasty patients. The antige n matching study (AMS) evaluated HLA matching in patients without circ ulating lymphocytotoxic antibody to HLA antigens and the cross-match s tudy (CS) evaluated the effect of using cross match-negative donors in patients with identified circulating lymphocytotoxic antibodies to HL A antigens. Sera from 510 patients considered for enrollment in the st udies were screened preoperatively for the presence of anti-class I ly mphocytotoxic antibodies (LA). The 42 patients (8%) found to have dete ctable LA entered the CS. The 468 patients found not to have detectabl e LA preoperatively entered the AMS. Fifteen of the 37 transplanted CS patients were found to have donor-specific anti-class I antibody (bef ore or after surgery). These patients were also screened for anti-clas s II LA and 25 had anti-class II panel reactive antibody greater than or equal to 5%. Forty-nine of the 419 transplanted AMS patients (12%) were found to have produced anti-class I LA after surgery, and in 19 p atients, antibody specificities were those of donor HLA antigens. Ther e was a significant association between the number of mismatched class I antigens and the number of donor-specific LA produced. The producti on of LA by AMS patients was significantly associated with reaction ep isodes; eighty-two percent of patients (40 of 49) with LA had reaction , compared with 63% of patients (230 of 365) without LA (P=0.02). Like wise, production of donor-specific LA was significantly associated wit h immune-mediated graft failure (P=0.025). For CS patients, there was no correlation between the production of donor-specific anti-class I o r nonspecific anti-class II antibodies and graft outcome. However, the CS patients had poorer graft survival than did AMS patients at 3 year s (57% vs, 66%, P=0.01). These data demonstrate that LA, especially di rected against donor class I HLA antigens following corneal transplant ation in high risk patients, are associated with immune graft rejectio n and can be an indicator of allograft rejection.