ANTI-HLA ANTIBODIES AND REJECTION TREATMENT MODALITY BOTH STRONGLY INFLUENCE GRAFT OUTCOME IN HIGH RISK CORNEAL TRANSPLANT RECEPIENTS.

Abstract

167 Fifty-five(55) corneal transplant candidates considered to be at high risk for graft failure were characterized by HLA typing of both donor and recepient and by determination of presence, isotype, HLA class I and/or class II specificity and anti- HLA specificity of pre-transplant antisera. These patients were then followed post-transplant at 1, 6, and 12 months postTx for the development of anti-HLA antibodies. Anti-rejection treatments were used in a non-blinded, non randomized fashion. Mild rejections were treated with topical steroids and higher risk patients were treated either with (1) Cyclosporine(PO dose adjusted to a blood level of 300 ng/ml) or (2) an intra-op IV bolus of120mg Solumedrol. Graft survival(GS) was calculated by the Kaplan-Meier method. Both the presence of preTx ABY (P<0.02) and the development of postTx ABY(P<0.0001) were strongly associated with decreased graft survival. Interestingly, IgM isotype antibody confered no increase risk(No ABy -1 yr GS=91%, IgM ABY-1yr GS=100%) Conversely IgG antibody decreased 1 year graft survival to 30%. Prior pregnancies and the% PRA had an insignificant effect. The choice of rejection treatment modality was also highly associated with graft outcome (Topical steroids, 1 yr GS=100%; IV steroids, 1 yr GS=20%; Cyclosporine, 1 yr GS=80%. P<0.0001) Since these were used based on the clinical opinion of degree of risk and/or severity of rejection episode, the data should be interpreted conservatively, e.g. the excellent outcomes in the topical steroid group are probably due to the mild degree of the reactions. The striking difference in efficacy between graft outcomes in patients treated with IV steroids vs Cyclosporine in this pilot study, however, strongly supports the initiation of a randomized trial. Interestingly also was the observation that the frequency of occurence of anti-HLA ABY was the same in both groups (%). This fact and the superior outcomes associated with the use ofCyclosporine also support a hypotheses that cellular as well as humoral immune responses may play a role in corneal graft rejection.