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ABDR AND AMINO ACID TRIPLET HLA MISMATCHES ARE ASSOCIATED WITH THE DEVELOPMENT OF ANTI-HLA ANTIBODIES AFTER RENAL TRANSPLANTATION.
Alin Girnita, MD, Rene Duquesnoy, PhD, Ron Shapiro, MD, Parmjeet Randhawa, MD, Joan Martell, BS, David Guaspari, BS, Anthony Demetris, MD and Adriana Zeevi, PhD. Pittsburgh PA, USA, UPMC, Pathology and Surgery.

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The aim of this study was to characterize the humoral allo-sensitization of renal transplant (RTX) recipients in the first year post-RTX.
The prospective screening of IgG anti-HLA specific alloantibodies (HLA-Ab) was performed by ELISA, and the DNA typing by SSO and SSP-PCR, for 79 RTX patients. The analysis of HLA mismatch at structural level was carried out by the HLAMatchmaker software.
HLA-Ab were detected in 21 (27%) patients in the first year post-RTX. 10/21 were de novo and 14/21 were donor-specific HLA-Ab. Five patients exhibited class I, 4 class II, and 12 class I and II HLA-Ab. Anti-class I HLA-Ab were detected earlier than anti-class II (average post-operative day 69 versus 244, p = 0.01). HLA-Ab were associated with increased prevalence of moderate and severe biopsy-proven acute rejection (ACR ≥ Banff grade 1B). 19/21 HLA-Ab producers had ACR, compared to 25/58 patients without HLA-Ab (p < 0.0005). The risk factors for developing HLA-Ab were: female recipient (11/21 vs 16/58, p < 0.05), Afro-American recipient (13/21 vs 6/58, p < 0.001), the number of ABDR mismatches (12% HLA-Ab producers in 0-1, 20% in 2-4, and 56% in 5-6 mismatched patients, p < 0.05), and polymorphisms in α1 and α2 chains of HLA class I molecule (amino acid triplets 10, 62, 76, 142-144, 149-151, p < 0.05).
The level of humoral sensitization increases with the time post-RTX and is associated with acute rejection. Although female and Afro-American recipients had increased frequency of HLA-Ab, the number of ABDR mismatches and the presence of particular polymorphisms in donor HLA molecules were the independent risk factors for humoral allosensitization.