Background Anti-HLA immunization measured as Panel Reactive Antibodies (PRA) is known to have a negative impact on patient and graft survival. The influence of pre-transplant peak PRA (pPRA) on immunologic outcome and the individual effects of anti-HLA class 1 and class 2 antibodies remain undetermined.

Methods We conducted a retrospective long-term study with inclusion of 1150 adult kidney transplant recipients (KTR) transplanted 1995-2014. None of the KTR had pretransplant donor specific antibodies (DSA). Demographics, clinical data and long-term outcomes over a period of maximal 20 years were assessed. Pretransplant peak PRA (pPRA) was determined using solid-phase essays Elisa and Luminex. HLA-immunization was defined as a pPRA >0%.

Results KTR with pre-transplant HLA immunization showed a significantly higher proportion of females, previous transplantations and longer time on dialysis. They were at a significantly higher risk for developing de novo DSA, antibody mediated rejections (ABMR), had a poorer death censored graft survival and a lower imputed cGFR. There was no significant difference in the incidence of T-cell mediated rejections (TCMR) or patient survival (Fig. 1 a-f). Cox proportional hazards models showed a significant association of pre-transplant immunization with development of de novo DSA (class 1 HR 2.57, p<0.001, class 2 HR 2.49, p<0.001), ABMR (class 1 HR 3.74, p<0.001, class 2 HR 2.36, p=0.025) and death censored graft loss (class 1 HR 2.49, p<0.001, class 2 HR 1.93, p=0.005). A multivariate model adjusted for recipient age, donor age, gender, time on dialysis, prior kidney transplantation, HLA-mismatches and cold ischemia time revealed only class 1 but not class 2 pre-transplant HLA immunization as an independent risk factor for de novo DSA, ABMR and death censored graft loss (HR 2.76, p<0.001, HR 4.16, p<0.001 and HR 2.07, p<0.001, respectively). There was no significant association with TCMR.

Conclusion Mainly non-donor-specific pre-transplant HLA class 1 immunization is an independent risk factor for the development of de novo DSA, ABMR and graft loss.

CITATION INFORMATION: Staeck O, Halleck F, Staeck A, Lehner L, Duerr M, Schrezenmeier E, Budde K, Khadzhynov D. Impact of Pretransplant Non-Donor-Specific HLA Immunization: Mainly Class 1 Immunization Leads to Poor Immunologic Outcome and Graft Loss. Am J Transplant. 2016;16 (suppl 3).

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