PMID- 22564585 OWN - NLM STAT- MEDLINE DCOM- 20120904 LR - 20120508 IS - 1873-2623 (Electronic) IS - 0041-1345 (Linking) VI - 44 IP - 4 DP - 2012 May TI - Role of killer immunoglobulin-like receptor-ligand interactions in human leukocyte antigen-matched sibling hematopoietic stem cell transplantation. PG - 919-21 LID - 10.1016/j.transproceed.2012.03.036 [doi] AB - 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 aplastic 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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Kanga, U AU - Kanga U AD - Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India. umakanga@hotmail.com FAU - Mourya, M AU - Mourya M FAU - Seth, T AU - Seth T FAU - George, J AU - George J FAU - Sood, P AU - Sood P FAU - Sharma, R AU - Sharma R FAU - Saxena, A AU - Saxena A FAU - Mehra, N K AU - Mehra NK LA - eng PT - Journal Article PL - United States TA - Transplant Proc JT - Transplantation proceedings JID - 0243532 RN - 0 (HLA Antigens) RN - 0 (Ligands) RN - 0 (Receptors, KIR) SB - IM MH - Acute Disease MH - Adult MH - Anemia, Aplastic/immunology/mortality/*surgery MH - Chronic Disease MH - Female MH - Gene Frequency MH - Graft vs Host Disease/genetics/immunology MH - HLA Antigens/genetics/*immunology MH - Haplotypes MH - Hematopoietic Stem Cell Transplantation/*adverse effects/mortality MH - *Histocompatibility MH - Histocompatibility Testing/methods MH - Humans MH - India MH - Leukemia/immunology/mortality/*surgery MH - Ligands MH - *Living Donors MH - Male MH - Myelodysplastic Syndromes/immunology/mortality/*surgery MH - Phenotype MH - Polymerase Chain Reaction MH - Receptors, KIR/genetics/*immunology MH - Recurrence MH - *Siblings MH - Time Factors MH - Treatment Outcome EDAT- 2012/05/09 06:00 MHDA- 2012/09/05 06:00 CRDT- 2012/05/09 06:00 PHST- 2012/05/09 06:00 [entrez] PHST- 2012/05/09 06:00 [pubmed] PHST- 2012/09/05 06:00 [medline] AID - S0041-1345(12)00256-4 [pii] AID - 10.1016/j.transproceed.2012.03.036 [doi] PST - ppublish SO - Transplant Proc. 2012 May;44(4):919-21. doi: 10.1016/j.transproceed.2012.03.036.