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.

doi.org/10.1038/bmt.2014.305, hdl.handle.net/1765/91606
Bone Marrow Transplantation
Erasmus MC: University Medical Center Rotterdam

Kosmoliaptsis, V, Jöris, M.M, Mallon, D.H, Lankester, A.C, von dem Borne, P.A.K, Kuball, J, … Claas, F.H.J. (2015). Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute GVHD following HSCT. Bone Marrow Transplantation, 50(4), 540–544. doi:10.1038/bmt.2014.305