DONOR-SPECIFIC ANTIBODY SHOWS RESTRICTED HLA-SPECIFICITY AMONG KIDNEY TRANSPLANT RECIPIENTS AND ARE OFTEN DETECTABLE ONLY AFTER ALLOGRAFT NEPHRECTOMY

 

 

0. Adeyj, M.Dl and R. J. Duquesnoy, Ph.D2

1. Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756-0001, USA

2. Division of Transplantation Pathology, University of Pittsburgh Medical Center, Pittsburgh 15213

 

This study deals with a serum analysis of patients whose kidney transplant from an HLA-A,B mismatched donor had failed and was removed by nephrectomy after the patient was placed on the waiting list for a second transplant. Many patients show an abrupt increase in the serum PRA following transplant nephrectomy. We interpret this finding that the patient had made donor-specific antibodies but they were undetectable because the kidney allograft had adsorbed them. We have conducted an HLAMatchmaker-based serum analysis to determine the specificities of antibodies detectable after nephrectomy. For each mismatched donor HLA antigen we determined the so-called triplotype. i.e. the combination of mismatched amino acid triplets in the HLA molecular sequence.  This analysis was designed to identify which mismatched triplets had elicited specific antibodies in the patient and which ones did not. Thus far, we have evaluated 30 transplant nephrectomy cases and all of them showed restricted patterns of antibody specificity. For instance, a patient with the J.n.A-Al, A30; B8,B18 phenotype was transplanted with a kidney mismatched for HLA-B13 or the 41T, 45Ma, 62Re, 76En, 80rTa, 82aLr, 144tQ1, 163E triplotype. Six months later, the kidney failed to function and the patient was put on the waiting list again. Three consecutive serum samples showed 1-4 % PRA and no HLA antibody could be detected. The patient underwent nephrectomy and the serum PRA went up to 60%. Serum analysis showed specific antibodies against the Bw4-associated 76En, 82aLr triplets. Other triplets 41T, 45Ma, 62Re and 163E did not react with patient antibodies and were apparently not immunogenic for this patient. The antibody specificity patterns are often restricted to a few triplets although the original donor has several mismatched HLA antigens. Antjgens with triplets recognized by patient antibodies must be considered as unacceptable mismatches. The appearance of donor-specific antibodies following nephrectomy may have considerable clinical significance:

(1.) Without nephrectomy, a patient's serum may show an incomplete antibody reactivity pattern because donor-specific antibodies are undetectable. This problem may interfere with the determination of HLA mismatch acceptability and the crossmatch when a new donor is being considered. This may help to explain why repeat transplants have lower success rates.

(2.) We must be very cautious with the post-transplant monitoring for donor-specific antibodies as prognostic or diagnostic indicators of rejection, because such antibodies may only be detected after removal of the failed transplant.