Aim: Patients who develop de novo donor-specific HLA antibodies (DSA) may have an increased risk of patient death and graft loss. We seek to examine factors that predict de novo DSA formation after liver transplantation (LT).

Methods: We analyzed 1099 adult LT recipients from 2000 to 2009 with a pre- and post-transplant serum sample available for DSA determination (83% of patients transplanted). All sera were analyzed for DSA using single antigen beads and MFIs >5000 were considered to be positive.

Results: 66% of patients were male, 73% were Caucasian, median age was 52. The most common indications for LT were HCV in 31%, HCC in 25%, and autoimmune conditions in 15%. 41% of patients received induction therapy. Immunosuppression at 1 year included tacrolimus 64%, MMF 50%, sirolimus 17%, and steroids 44% of the time. De novo DSA was observed in 7.8% of patients (0.2% only class I, 7.5% only class II, and 0.1% both classes). Multivariable logistic regression analysis found that HLA-DQ mismatches, cyclosporine as compared to tacrolimus, and African-American (AA) recipient race had an increased likelihood of de novo DSA formation, while MELD score >15 had a lower likelihood of de novo DSA formation (Table). Patients with HLA-DQ mismatches had significantly higher rates of de novo DSA production compared to other HLA locus mismatches (Fig A). This effect was observed in a dose-dependent manner but it was only significantly different for HLA-DQ mismatches (Fig B). Mismatches to DQ2, DQ7 and DQ8 showed the highest rates of de novo DSA production.

Conclusions: De novo DSA development is associated with the number of HLA-DQ mismatches, the use of cyclosporine, AA recipient race, and low MELD score. Patients transplanted with DQ mismatches may benefit from tacrolimus based immunosuppression and closer monitoring.

BaÑuelos, N.: Employee, One Lambda, Inc. Terasaki, P.: Stockholder, One Lambda, Inc.

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