Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: A novel predictive algorithm

Roberto Littera, Nicola Orrù, Giovanni Caocci, Marco Sanna, Marina Mulargia, Eugenia Piras, Adriana Vacca, Claudio Giardini, Maria G. Orofino, Giuseppe Visani, Alice Bertaina, Giovanna Giorgiani, Franco Locatelli, Carlo Carcassi, Giorgio La Nasa

Research output: Contribution to journalArticlepeer-review

Abstract

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4·2, 95% confidence interval (CI) 1·7-10·1, P=0·002] and transplantation-related mortality (HR 4·7, 95% CI 1·6-14·2, P=0·01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6·1, 95% CI 1·9-19·2, P=0·002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6·8, 95% CI 1·9-24·4, P=0·005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making.

Original languageEnglish
Pages (from-to)118-128
Number of pages11
JournalBritish Journal of Haematology
Volume156
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Activating killer immunoglobulin-like receptor genes
  • Donor selection algorithm
  • Graft-versus-host disease
  • Haematopoietic stem cell transplantation
  • HLA-C KIR ligands

ASJC Scopus subject areas

  • Hematology

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