Ab. Hahn et al., THE ASSOCIATION OF LYMPHOCYTOTOXIC ANTIBODIES WITH CORNEAL ALLOGRAFT-REJECTION IN HIGH-RISK PATIENTS, Transplantation, 59(1), 1995, pp. 21-27
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.