Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT

V Kosmoliaptsis, MM (M.) Joris, DH Mallon, AC Lankester, PA von dem Borne, J Kuball, M Bierings, Jan Cornelissen, Marlies Sijnke, Ronnie van der Holt, JA Bradley, M Oudshoorn, JJ van Rood, CJ Taylor, FHJ Claas

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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 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.
Original languageUndefined/Unknown
Pages (from-to)540-544
Number of pages5
JournalBone Marrow Transplantation
Issue number4
Publication statusPublished - 2015

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