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RESEARCH PRODUCT

Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study

Xiaojiang GaoMaureen P. MartinYing QiDenise WhitbyCarmela LauriaMary CarringtonJames J. GoedertVitale Francesco

subject

0301 basic medicineGenotypevirusescase-control studyPopulationchemical and pharmacologic phenomenaHuman leukocyte antigenBiologyLymphocyte ActivationSettore MED/42 - Igiene Generale E ApplicataMajor Articles and Brief Reports03 medical and health sciencesReceptors KIRnatural killer–cell immunoglobulin-like receptorsHLA AntigensRisk FactorsSeroepidemiologic Studieshuman leukocyte antigenGenotypeotorhinolaryngologic diseasesHLA-B AntigensHumansImmunology and AllergySeroprevalenceGenetic Predisposition to Diseasehuman geneticeducationSarcoma Kaposieducation.field_of_studyClassic Kaposi SarcomaCase-control studyvirus diseasesKaposi sarcomaOdds ratiomajor histocompatibility complex030104 developmental biologyInfectious DiseasesGene Expression RegulationItalyCase-Control StudiesItaly; Kaposi sarcoma; case-control study; human genetics; human leukocyte antigens; major histocompatibility complex; natural killer–cell immunoglobulin-like receptorsHerpesvirus 8 HumanImmunology

description

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs.

yearjournalcountryeditionlanguage
2015-08-12Journal of Infectious Diseases
https://doi.org/10.1093/infdis/jiv413