Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT
Kosmoliaptsis, V.; Joris, M. M.; Mallon, D. H.; Lankester, A. C.; von dem Borne, P. A.; Kuball, J.; Bierings, M.; Cornelissen, J. J.; Groenendijk-Sijnke, M. E.; van der Holt, B.; Bradley, J. A.; Oudshoorn, M.; van Rood, J. J.; Taylor, C. J.; Claas, F. H. J.
(2015) Bone Marrow Transplantation, volume 50, issue 4, pp. 540 - 544
(Article)
Abstract
We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n = 171) and 10/10 HLA-A-, -B-, -C-, -DRB1-and -DQB1-matched
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grafts (n = 168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of. grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.
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Keywords: T-CELL ALLOREACTIVITY, TRANSPLANTATION, RESOLUTION, ALGORITHM, VITRO, IMMUNOGENICITY, PREDICTION, MOLECULES, PEPTIDE, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
ISSN: 0268-3369
Publisher: Nature Publishing Group
(Peer reviewed)