HLA-DP antibodies before and after renal transplantation

• Published in: Tissue antigens Vol. 75; no. 3; pp. 278 - 285
• Main Authors: Billen, E. V. A., Christiaans, M. H. L., Doxiadis, I. I. N., Voorter, C. E. M., Van Den Berg-Loonen, E. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2010
• Subjects: Antibodies - immunology; Antibody Formation - immunology; Case-Control Studies; Complementarity Determining Regions - immunology; Epitopes - analysis; Epitopes - immunology; Female; HLA-DP alpha-Chains; HLA-DP Antigens - immunology; human leukocyte antigen class II; human leukocyte antigen-DP; Humans; humoral antibodies; Kidney Transplantation - immunology; Male; renal transplantation; Tissue Donors
• ISSN: 0001-2815; 1399-0039
• DOI: 10.1111/j.1399-0039.2009.01428.x

Human leukocyte antigen (HLA)‐DP is considered a target for humoral immune response in clinical transplantation. This study analyses the incidence of HLA‐DP antibodies in renal patients. Development and epitope specificity of donor‐specific antibodies (DSA) and non‐DSA (NDSA) were examined. Pre‐ and posttransplant sera of 338 patients were screened for HLA‐DP antibodies using the luminex single antigen assay. Positive patients, partners and/or kidney donors were HLA‐DP typed by sequence‐specific oligonucleotides. Potential epitopes were mapped by comparing the amino acid sequences of HLA‐DP hypervariable regions (HVR) A–F of recipient, partner and/or donor. Specificities in the sera were aligned to deduce the HVR motif responsible for the antibodies. HLA‐DP antibodies were detected in 14% of the patients (48/338). Before transplantation, the antibodies were shown in 23% (10 females and 1 male) and 77% were found after transplantation (30 in patients after the first, 7 after the second graft). Specificities were never restricted to individual mismatched antigens; broad HLA‐DP sensitization was found as a rule. A single HVR mismatch was present in 80% of the DSA and in 79% of the NDSA. No HLA‐DPA specific antibodies were found. Our findings confirm that HLA‐DP antibodies are specific for epitopes shared by different HLA‐DP antigens, indicating that only a restricted number of mismatched epitopes are recognized by the recipients immune system. Matching for immunogenic HLA‐DP epitopes for renal transplantation seems to be functionally more relevant than classical matching at the allelic level.