PMID- 12660520
OWN - NLM
STAT- MEDLINE
DCOM- 20030428
LR  - 20071114
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 75
IP  - 6
DP  - 2003 Mar 27
TI  - HLAmatchmaker: a molecularly based algorithm for histocompatibility 
      determination. IV. An alternative strategy to increase the number of compatible 
      donors for highly sensitized patients.
PG  - 889-97
AB  - BACKGROUND: HLAMatchmaker is a computer algorithm that determines human leukocyte 
      antigen (HLA) compatibility at the level of polymorphic amino acid triplets in 
      antibody-accessible sequence positions. Recent studies have shown that 
      HLA-DR-matched kidney transplant recipients with zero to two triplet mismatches 
      had almost identical graft survival rates as those with zero HLA-A,B,DR antigen 
      mismatches. This report describes how HLAMatchmaker can be used to identify more 
      compatible donors for highly sensitized patients. METHODS: The HLAMatchmaker 
      program was used to calculate the probability of finding a donor (PFD) with zero, 
      one, or two triplet mismatches for 54 highly sensitized patients waiting for a 
      kidney transplant and having panel reactive antibody (PRA) values greater than 
      85% and 50 randomly selected nonsensitized patients with PRA values less than 3%. 
      RESULTS: There was a wide variability for PFD values for the two patient cohorts. 
      If only donors with zero HLA-A,B mismatches were deemed acceptable for 
      recipients, the median PFD of a zero-antigen mismatch was 0.046% for 
      nonsensitized patients and 0.009% for highly sensitized patients (P=0.007). Half 
      of the highly sensitized patients had a PFD below 0.01%, or fewer than 1 in 
      10,000 donors would have zero antigen mismatches. Application of HLAMatchmaker 
      identified additional HLA antigens with zero-triplet mismatches for 27 patients, 
      resulting in a 1.8-fold increase in PFD. Considering additional antigens with 
      one-triplet or two-triplet mismatches increased the PFD by an additional 3.8-fold 
      and 13.7-fold, respectively. Acceptable antigen mismatches for 37 of the 54 
      highly sensitized patients were identified by consistently negative reactions in 
      serum screens, and their addition resulted in a 12.7-fold increase of the PFD to 
      a median of 0.141%. Applying these acceptable antigens to the HLAMatchmaker 
      algorithm identified additional antigens with zero or acceptable triplet 
      mismatches and their inclusion increased the PFD by 3.3-fold to 0.347%. 
      CONCLUSIONS: HLAMatchmaker offers a valuable strategy for identifying more 
      suitably HLA-matched donors and has the potential for alleviating the problem of 
      accumulation of highly sensitized patients on the transplant waiting list.
FAU - Duquesnoy, Rene J
AU  - Duquesnoy RJ
AD  - University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. 
      duquesnoyr@msx.upmc.edu.
FAU - Howe, Judy
AU  - Howe J
FAU - Takemoto, Steve
AU  - Takemoto S
LA  - eng
GR  - R01 DK-52803/DK/NIDDK NIH HHS/United States
GR  - R01 DK-54928/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Algorithms
MH  - Amino Acid Sequence
MH  - Autoantibodies/blood
MH  - Databases, Factual
MH  - Graft Survival/immunology
MH  - HLA-A Antigens/*analysis/chemistry/immunology
MH  - HLA-B Antigens/*analysis/chemistry/immunology
MH  - Histocompatibility Testing/*methods
MH  - Humans
MH  - Molecular Sequence Data
MH  - Tissue Donors
MH  - *Tissue and Organ Procurement
EDAT- 2003/03/28 05:00
MHDA- 2003/04/29 05:00
CRDT- 2003/03/28 05:00
PHST- 2003/03/28 05:00 [pubmed]
PHST- 2003/04/29 05:00 [medline]
PHST- 2003/03/28 05:00 [entrez]
AID - 10.1097/01.TP.0000055097.58209.83 [doi]
PST - ppublish
SO  - Transplantation. 2003 Mar 27;75(6):889-97. doi: 
      10.1097/01.TP.0000055097.58209.83.