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- Title
Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study.
- Authors
Goedert, James J.; Martin, Maureen P.; Vitale, Francesco; Lauria, Carmela; Whitby, Denise; Ying Qi; Xiaojiang Gao; Carrington, Mary; Qi, Ying; Gao, Xiaojiang
- Abstract
<bold>Background: </bold>Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS.<bold>Methods: </bold>In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals.<bold>Results: </bold>In both the discovery and validation cohorts, KS was associated with HLA-A*11:01 (adjusted OR for the combined cohorts, 0.4; P = .002) and HLA-C*07:01 (adjusted OR, 1.6; P = .002). Consistent associations across cohorts were also observed with activating KIR3DS1 plus HLA-B Bw4-80I and homozygosity for HLA-C group 1. With KIR3DS1 plus HLA-B Bw4-80I, the KSHV seroprevalence was 40% lower (adjusted OR for the combined cohorts, 0.6; P = .01), but the KS risk was 2-fold higher (adjusted OR, 2.1; P = .002). Similarly, the KSHV seroprevalence was 40% lower (adjusted OR, 0.6; P = .01) but the KS risk 80% higher with HLA-C group 1 homozygosity (adjusted OR, 1.8; P = .005).<bold>Conclusions: </bold>KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs.
- Subjects
KAPOSI'S sarcoma; IMMUNOGLOBULIN receptors; LEUCOCYTES; ANTIGENS; CASE-control method; HUMAN genetics; MAJOR histocompatibility complex; KILLER cells; CELL receptors; DISEASE susceptibility; EPIDEMIOLOGICAL research; GENES; HERPESVIRUSES; IMMUNOLOGY technique; RESEARCH funding; HLA-B27 antigen; GENOTYPES
- Publication
Journal of Infectious Diseases, 2016, Vol 213, Issue 3, p432
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiv413