Title
The role of KIR gene content and HLA-C group in susceptibility to HTLV-1-associated myelopathy / tropical spastic paraparesis in Peru The role of KIR gene content and HLA-C group in susceptibility to HTLV-1-associated myelopathy / tropical spastic paraparesis in Peru
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
New York ,
Subject
Human medicine
Source (journal)
Human immunology. - New York
Volume/pages
(2010)
ISSN
0198-8859
ISI
000280455800011
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) affects approximately 5% of HTLV-1-infected individuals. It is poorly understood why only some infected subjects develop this disease, but host genetic factors may determine susceptibility. The innate immune system may influence disease outcome in HTLV-1-infected subjects because of its role in early immune responses to viral infections. Variation in genes encoding killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) molecule ligands may affect the risk of HAM/TSP. We performed a two-stage case-control study to examine the distribution of KIR genes and HLA-Cw groups in Peruvian HTLV-1-infected HAM/TSP subjects and asymptomatic carriers. We also tested for epistatic effects between specific KIR genes and HLA-Cw groups. In the first stage, we found several trends towards association with HAM/TSP or proviral load (PVL). However, these results were not replicated in the second stage. In conclusion, this is the first report on KIR gene frequencies in the Peruvian population and may be of significance in hematopoietic stem-cell transplants. Our study did not reveal significant associations between KIR genes and HLA-Cw groups and HAM/TSP or PVL. However, since our study was only powered to detect larger effects, additional studies using larger cohorts are needed.
Human T-lymphotropic virus 1 (HTLV-1)associated myelopathy/tropical spastic paraparesis (HAM/TSP) affects approximately 5% of HTLV-1infected individuals. It is poorly understood why only some infected subjects develop this disease, but host genetic factors may determine susceptibility. The innate immune system may influence disease outcome in HTLV-1infected individuals because of its role in early immune responses to viral infections. Variation in genes encoding killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) molecule ligands may affect the risk of HAM/TSP. We performed a two-stage case-control study to examine the distribution of KIR genes and HLA-Cw groups in Peruvian HTLV-1infected HAM/TSP individuals and asymptomatic carriers. We also tested for epistatic effects between specific KIR genes and HLA-Cw groups. In the first stage, we found several trends toward association with HAM/TSP or proviral load (PVL). However, these results were not replicated in the second stage. In conclusion, this is the first report on KIR gene frequencies in the Peruvian population and may be of significance in hematopoietic stem-cell transplants. Our study did not reveal significant associations between KIR genes and HLA-Cw groups and HAM/TSP or PVL. However, because our study was powered to detect only larger effects, additional studies using larger cohorts are needed. 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights
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