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.
Keywords: Italy; Kaposi sarcoma; case-control study; human genetics; human leukocyte antigens; major histocompatibility complex; natural killer–cell immunoglobulin-like receptors.
Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.