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ESTIMATING THE SEVERITY OF HLA MISMATCHES BY THE WEB-ACCESSIBLE HISTOCHECK TOOL.
Holger-A. Elsner MD, PhD , David DeLuca , Joachim Strub and Rainer Blasczyk MD, PhD . Hannover Germany, Hannover Medical School, D-30625, Department of Transfusion Medicine .
HLA polymorphism is a major barrier for hematopoietic stem cell and solid organ transplantation. To estimate the allogeneic potential between HLA mismatched stem cell donor/recipient pairs, we recently proposed a matching score (dissimilarity index), that is based on structural data of HLA class I molecules, and on functional similarity of amino acids. This first approach revealed new features about presumptive subtype allogenicities within the HLA-A*23 and A*24 groups. We now have developed an internet-based software tool ("HistoCheck") that is capable to assess the allogenicity (matching score) between any pair of HLA class I and also class II alleles. Newly described HLA sequences will be regularly integrated into the database according to the updates of the nomenclature for factors of the HLA system. The software is intended to be a first step for estimating the allogenicity of HLA mismatches in peculiar clinical settings, as long as there are no reliable in vitro or clinical studies available. The algorithm can later be modified according to functional data, e.g. peptide binding specificities. With the extension of the sequence similarity concept to all relevant HLA class I and II loci, the HistoCheck software may contribute to prevent HLA mismatching being a matter of chance.