Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natural killer cell receptor KIR3DS1 is associated with improved outcome in malignancies, infections, and autoimmune diseases, but data for the impact of KIR3DS1 in HSCT are inconsistent. Using genomic DNA from the National Marrow Donor Program, we performed donor KIR genotyping for 1087 patients who received an unrelated hematopoietic stem cell transplantation. A total of 33% of donors were KIR3DS1(+). Compared with KIR3DS1(-) donors, donor KIR3DS1 was associated with lower-grade II-IV acute graft-versus-host disease (GVHD; odds ratio = 0.71; 95% confidence interval, 0.55-0.92; P = .009), but not with relapse (hazard ratio = 0.97; 95% confidence interval, 0.73-1.29; P = .82). Furthermore, grade II-IV acute GVHD, overall mortality, and transplantation-related mortality all decreased as the number of copies of donor KIR3DS1 increased (P = .007, P = .03, and P = .02, respectively), with the lowest failure rate occurring among patients homozygous for donor KIR3DS1. Selection of donors with KIR3DS1 may decrease acute GVHD without compromising relapse-free survival, separating the graft-versus-tumor effect from unwanted GVHD.
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PMID:Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation. 2012 16

The function of natural killer (NK) cells is controlled by several activating and inhibitory receptors, including the family of killer-immunoglobulin-like receptors (KIRs). One distinctive feature of KIRs is the extensive number of various haplotypes generated by the gene content within the KIR gene locus as well as by highly polymorphic members of the KIR gene family, namely KIR3DL1/S1. Within the KIR3DL1/S1 gene locus, KIR3DS1 represents a conserved allelic variant and displays other unique features in comparison to the highly polymorphic KIR3DL1 allele. KIR3DS1 is present in all human populations and belongs to the KIR haplotype group B. KIR3DS1 encodes for an activating receptor featuring the characteristic short cytoplasmic tail and a positively charged residue within the transmembrane domain, which allows recruitment of the ITAM-bearing adaptor molecule DAP12. Although HLA class I molecules are thought to represent natural KIR ligands, and HLA-Bw4 molecules serve as ligands for KIR3DL1, the ligand for KIR3DS1 still needs to be identified. Despite the lack of formal evidence for an interaction of KIR3DS1 with HLA-Bw4-I80 or any other HLA class I subtype to date, a growing number of associations between the presence of KIR3DS1 and the outcome of viral infections have been described. Especially, the potential protective role of KIR3DS1 in combination with HLA-Bw4-I80 in the context of HIV-1 infection has been studied intensively. In addition, a number of recent studies have associated the presence or absence of KIR3DS1 with the occurrence and outcome of some malignancies, autoimmune diseases, and graft-versus-host disease (GVHD). In this review, we summarize the present knowledge regarding the characteristics of KIRD3S1 and discuss its role in various human diseases.
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PMID:Role of KIR3DS1 in human diseases. 2312 43