High MFI De Novo MHC Class II Donor Specific Antibody Formation Impairs Patient Survival after Liver Transplantation

Abstract

Aim: To determine the predictors of and subsequent incidence and consequence of de novo MHC class I & II donor specific antibody (DSA) formation after liver transplantation (LT). Methods: Since 1985, our biorepository prospectively collects protocol serum samples from all donors and recipients of LT in conjunction with a clinical and laboratory research database. 760 consecutive primary LT patients who had a pre-LT serum sample and a 1-year post-LT serum sample from 1/01-5/09 were blinded and analyzed for HLA DSA using LABScreen® single antigen beads test. For this analysis patients with high MFI (>5000) DSA were compared to patients without DSA (< 1000). Results: 64% of patients were male and 67% were Caucasian with a median recipient and donor age of 51 and 40 respectively. 32% of patients had HCV as their primary diagnosis. Only 9 patients developed de novo class I DSA (1.2%), but 119 patients developed de novo class II DSA (15.7%) at their 1-year follow-up. Immunosuppression had no effect on de novo class I DSA formation. High MFI class II DSA formation had a profound effect on graft (P< 0.001) and patient survival (P< 0.001). Multivariable Cox regression analysis controlling for donor and recipient age, HCV diagnosis, CMV and ACR found that de novo class II DSA is an independent predictor of death with a hazards ratio of 2.47 (P< 0.001). A multivariable logistic regression analysis found cyclosporine use as opposed to tacrolimus (OR=3.21; P< 0.001) and AA race (OR= 2.74; P = 0.02) as the only 2 independent predictors of de novo high MFI class II DSA formation. Conclusion: High MFI (>5000) de novo class II DSA formation is strongly associated with cyclosporine use and AA race and is an independent predictor of death after liver transplantation.[Figure 1]