Physiochemical Disparity of Mismatched HLA Class I Alloantigens and Risk of Acute GVHD Following HSCT

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2015 Jan 27

PMID 25621806

Citations 4

Authors

V Kosmoliaptsis

M M Joris

D H Mallon

A C Lankester

P A von dem Borne

J Kuball

M Bierings

J J Cornelissen

M E Groenendijk-Sijnke

B van der Holt

J A Bradley

M Oudshoorn

J J van Rood

C J Taylor

F H J Claas

Affiliations

Soon will be listed here.

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 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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