Role of killer immunoglobulin-like receptor–ligand interactions in human leukocyte antigen–matched sibling hematopoietic stem cell transplantation

Uma Kanga, Manish Mourya, Tulika Seth, J George, Prashant Sood, R Sharma, A Saxena, NK Mehra

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Introduction. Killer immunoglobulin-like receptor (KIR)-ligand mismatches lead to natural killer cell alloreactivity after hematopoietic stem cell transplantation (HSCT). However, their clinical impact on HSCT outcomes is controversial due to complexity of KIR haplotypes, genotypes, and phenotypes as well as their diversity among patient populations. The present study investigated the role of KIR-ligand interactions in human leukocyte antigen (HLA)-matched sibling transplants.
Methods. The recipient cohort, which included patients diagnosed with a plastic anemia, acute leukemia, and myelodysplastic syndrome, received granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells. HLA typing was performed using polymerase chain reaction - sequence specific oligo probes (PCR-SSO). The KIR genotype of the donors and the ligands C1 (Asparagine 80), C2 (Lysine 80), and Bw4 recipient typings were performed
using polymerase chain reaction - sequence specific primers (PCR-SSP). We assessed acute and chronic graft-versus-host disease (GVHD), relapse, and overall survival.
Results. While 84.5% of donors carried a Bx KIR, 15.5% carried the AA haplotype. The effect of a recipient’s lack of ligands among 88.5% of cases was associated with 39% of subjects developing GvHD. Lack of C1 may lead to manifestations of acute GvHD and lack of C2 to manifestation of chronic GvHD. The presence of both C1 and C2 seemed to be protective against both forms of GvHD. The role of two Bw4 alleles, threonine (T) or isoleucine (I) at position 80, was evaluated. 73% of recipients who carried Bw4 80(I) versus 27% with the Bw4 80(T) allele. The presence of Bw4-80(T) allele appeared to reduce the risk of GvHD, indicating its stronger inhibitory effect than its 80(I) counterpart.
Conclusion. KIR-ligand interactions influenced HSCT outcomes.
Original languageEnglish
Pages (from-to)919-921
Number of pages3
JournalTransplantation Proceedings
Volume44
Issue number4
Early online date10 May 2012
DOIs
Publication statusPublished - May 2012

Keywords

  • HLA ANTIGENS

Fingerprint Dive into the research topics of 'Role of killer immunoglobulin-like receptor–ligand interactions in human leukocyte antigen–matched sibling hematopoietic stem cell transplantation'. Together they form a unique fingerprint.

  • Cite this