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HLA, KIR frequencies indicate risk for Kaposi sarcoma, KSHV
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Researchers have acquired a new understanding of the disease pathogenesis of Kaposi sarcoma-associated herpesvirus infection through evaluating the interactions between human leukocyte antigen and killer-cell immunoglobulin-like receptor ligand pairs.
“Human leukocyte antigen (HLA) and related genes are centrally involved in immunological response to infectious diseases and thus would be expected to affect the risk of developing [Kaposi sarcoma-associated herpesvirus (KSHV)] infection or Kaposi sarcoma,” the researchers wrote. “Only tenuous support for this hypothesis has been reported.”
The researchers conducted population-based case-control studies to test whether HLA and killer-cell immunoglobulin-like receptor ligand (KIR) affect the risk for KSHV or Kaposi sarcoma. They compared HLA class I and KIR gene frequencies in 250 classic Kaposi sarcoma cases without AIDS, 280 KSHV-seropositive controls, 576 KSHV-seronegative controls and 24 KSHV-seroindeterminant controls.
In phase 1, researchers compared KSHV-seropositive controls with seronegative controls to determine a possible association between KSHV seroprevalence and each HLA-A, HLA-B and HLA-C allele and KIR gene. Four genes were associated with seroprevalence, but these findings were not replicated in phase 2. Therefore, researchers pooled the KSHV-seropositive and seronegative control groups and compared them with the classic Kaposi sarcoma cases for single HLA alleles and KIR genes.
Compared with controls, classic Kaposi sarcoma was associated with a decrease in HLA-A*11:01 frequency (adjusted OR = 0.4; 95% CI, 0.2-0.7). However, participants carrying HLA-C*07:01 were at higher risk for the disease (aOR = 1.6; 95% CI, 1.2-2.1). There was no association with any of the other HLA alleles or KIR genes.
KSHV seroprevalence was 40% lower with KIR3DS1 plus HLA-B Bw4-80I (adjusted OR = 0.6; 95% CI, 0.4-0.9). However, Kaposi sarcoma was twofold higher with this combination (adjusted OR = 2.1; 95% CI, 1.3-3.4). KSHV seroprevalence also was 40% lower with HLA-C group 1 homozygosity (adjusted OR = 0.6; 95% CI, 0.4-0.9), but Kaposi sarcoma risk was 80% higher (adjusted OR = 1.8; 95% CI, 1.2-2.7).
“These associations suggest that this compound genotype confers protection against KSHV infection, but among those who do become infected, there is an increased risk of developing classic Kaposi sarcoma,” the researchers wrote. – by Tina DiMarcantonio
Disclosure: The researchers report no relevant financial disclosures.
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