PMID- 16699463 OWN - NLM STAT- MEDLINE DCOM- 20060626 LR - 20060515 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 81 IP - 9 DP - 2006 May 15 TI - Utility of HLAMatchmaker and single-antigen HLA-antibody detection beads for identification of acceptable mismatches in highly sensitized patients awaiting kidney transplantation. PG - 1331-6 AB - BACKGROUND: In highly sensitized patients (HSP) awaiting renal transplantation, accurate delineation of acceptable human leukocyte antigen (HLA) mismatches (AMM) aids identification of suitable crossmatch negative donors. Comparison of differences in polymorphic triplet amino acid sequences in antibody accessible regions of HLA may predict immunogenicity. We have examined the ability of the HLAMatchmaker computer algorithm to predict AMM determined by antibody screening using the full repertoire of single-antigen HLA-A and -B specificities. METHODS: The HLA types of 24 HSP awaiting kidney transplantation were analyzed using HLAMatchmaker to determine the number of triplet amino acid (TAA) mismatches for each of 64 mismatched HLA-A and -B specificities. Patient sera with the highest immunoglobulin (Ig)G HLA-specific antibody reactivity were tested against the 64 individual HLA-A and -B specificities using single-antigen HLA antibody detection beads. Logistic regression analysis was performed to determine the association between AMM and the number of TAA mismatches. RESULTS: There was a strong positive association between the number of TAA mismatches and the presence of HLA-specific antibody. HLA specificities with zero TAA mismatches were antibody positive in only 4 of 47 (9%) cases. A single TAA mismatches was sufficient to invoke an antibody response in 40 (41%) of 98 cases, increasing to 97 (87%) of 112 cases with 9 or more TAA mismatches. However, there was considerable heterogeneity between individual patients, and only 16 (67%) of the 24 HSP studied fitted the logistic regression model for TAA mismatches and HLA-specific antibody. CONCLUSIONS: Identification of TAA mismatches using HLAMatchmaker is a helpful tool for predicting potential donors with an acceptable HLA mismatch in HSP. FAU - Goodman, Reyna S AU - Goodman RS AD - Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. FAU - Taylor, Craig J AU - Taylor CJ FAU - O'Rourke, Cheryl M AU - O'Rourke CM FAU - Lynch, Andrew AU - Lynch A FAU - Bradley, J Andrew AU - Bradley JA FAU - Key, Tim AU - Key T LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antigen-Antibody Complex) RN - 0 (HLA Antigens) RN - 0 (HLA-A Antigens) RN - 0 (HLA-B Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Isoantibodies) SB - IM MH - Adult MH - Amino Acid Sequence MH - Antigen-Antibody Complex MH - Blood Transfusion MH - Female MH - HLA Antigens/*immunology MH - HLA-A Antigens/immunology MH - HLA-B Antigens/immunology MH - Histocompatibility Antigens Class I/*immunology MH - Histocompatibility Testing/*methods MH - Humans MH - Immunization/methods MH - Isoantibodies/*blood MH - Kidney Transplantation/*immunology MH - Male MH - Middle Aged MH - Regression Analysis MH - Reoperation/statistics & numerical data MH - *Waiting Lists EDAT- 2006/05/16 09:00 MHDA- 2006/06/27 09:00 CRDT- 2006/05/16 09:00 PHST- 2006/05/16 09:00 [pubmed] PHST- 2006/06/27 09:00 [medline] PHST- 2006/05/16 09:00 [entrez] AID - 00007890-200605150-00018 [pii] AID - 10.1097/01.tp.0000205202.56915.f5 [doi] PST - ppublish SO - Transplantation. 2006 May 15;81(9):1331-6. doi: 10.1097/01.tp.0000205202.56915.f5.