0000000000275489
AUTHOR
Carmela Lauria
A Multiplex Panel of Plasma Markers of Immunity and Inflammation in Classical Kaposi Sarcoma
Kaposi sarcoma (KS) risk is affected by perturbed immunity. Herein, we compared plasma from 15 human immunodeficiency virus (HIV)–negative classic KS cases to plasma from 29 matched controls, using a multiplex panel of immunity markers. Of 70 markers, CXCL10 (IP-10), sIL-1RII, sIL-2RA, and CCL3 (MIP-1A) were strongly and significantly associated with KS, after adjustment for age and smoking status. These and previous observations are consistent with a tumor-promoting role for these cytokines, particularly CXCL10, but the small sample size and case-control design preclude firm conclusions on KS risk or pathogenesis. Larger, well-designed prospective studies are needed to better assess the as…
Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study
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. RESUL…
Risk factors for classical Kaposi's sarcoma.
Background: Classical Kaposi's sarcoma (KS) is a malignancy of lymphatic endothelial skin cells. Although all forms of KS are associated with the KS-associated herpesvirus (KSHV), classical KS occurs in a small fraction of KSHV-infected people. We sought to identify risk factors for classical KS in KSHV-infected individuals. Methods: Lifestyle and medical history data from case patients with biopsyproven non-AIDS (non-acquired immunodeficiency syndrome) KS in Italy were compared by logistic regression analysis with data from population-based KSHV-seropositive control subjects of comparable age and sex. After KSHV immunofluorescence testing, randomly selected patients on the rosters of local…
Risk of classic Kaposi sarcoma with residential exposure to volcanic and related soils in Sicily
Purpose Before AIDS, endemic (African) Kaposi sarcoma (KS) was noted to occur in volcanic areas and was postulated to result from dirt chronically embedded in the skin of the lower extremities. The primary cause of all KS types is KS-associated herpesvirus (KSHV) infection, but cofactors contribute to the neoplasia. We investigated whether residential exposure to volcanic or related soils was associated with the risk of classic Kaposi sarcoma (cKS) in Sicily. Methods Risk of incident cKS ( N = 141) compared with population-based KSHV seropositive controls ( N = 123) was estimated for residential exposure to four types of soil, categorized with maps from the European Soil Database and dire…
Host immunogenetics and control of human herpesvirus-8 infection
BACKGROUND: Kaposi sarcoma (KS) is primarily caused by human herpesvirus (HHV)-8 infection, and the risk is increased with high HHV-8 lytic or latent antibody titers or the detection of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs). Host genes important for control of HHV-8 infection are not well characterized. METHODS: In 172 HHV-8 latent nuclear antigen (LANA)-seropositive adults in Italy without KS, we examined correlations of common variants in host immune genes with the detection of HHV-8 DNA in PBMCs and with high lytic and latent antibody titers. Twenty-eight single-nucleotide polymorphisms in 14 genes were analyzed. We detected HHV-8 DNA in PBMCs with real-time amplificati…
Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily
Abstract Background Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS). Methods In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposu…
Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.
BACKGROUND Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum β-2-microglobulin and neopterin levels. METHODS Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detec…
Risk Factors for Classical Kaposi Sarcoma in a Population-based Case-control Study in Sicily
Abstract Background: Classical Kaposi sarcoma is a rare complication of Kaposi sarcoma-associated herpes virus (KSHV) infection. We conducted a population-based, frequency-matched case-control study in Sicily to further investigate the reported inverse relationship between smoking and classical Kaposi sarcoma and to identify other factors associated with altered risk. Methods: All incident, histologically confirmed classical Kaposi sarcoma cases in Sicily were eligible. A two-stage cluster sample design was applied to select population controls. KSHV seropositivity was determined using four antibody assays (K8.1 and orf73 enzyme immunoassays and two immunofluorenscence assays). Using SAS-ca…
A Common Genetic Variant inFCGR3A-V158F and Risk of Kaposi Sarcoma Herpesvirus Infection and Classic Kaposi Sarcoma
Associations of FCGR3A among men with HIV/acquired immunodeficiency syndrome suggest that host responses affect the pathogenesis of Kaposi sarcoma herpesvirus (KSHV) infection and risk of acquired immunodeficiency syndrome – associated Kaposi sarcoma. Using DNA from two HIV seronegative case-control populations in Italy, we examined whether the functional FCGR3A-V158F variant was associated with risk of KSHV infection or classic Kaposi sarcoma (CKS). In population I, we examined FCGR3A variants and risk of KSHV infection in 34 KSHV latent nuclear antigen (LANA)-seropositive and 120 LANAseronegative adults from Sardinia (52% male; median age, 45 years; range, 31-60), whereas in population II…
Socio-economic and other correlates of Kaposi sarcoma-associated herpesvirus seroprevalence among older adults in Sicily.
The virus that causes Kaposi sarcoma, KS-associated herpesvirus (KSHV, also known as human herpesvirus 8) has an unusual distribution and poorly characterized modes of transmission. To clarify these issues, socio-demographic correlates of KSHV seroprevalence were examined in a population-based study. In 1,154 randomly sampled adults (aged 32- 92, mean 71 years) throughout Sicily, KSHV antibodies were detected with four assays and a conservative algorithm. Seroprevalence was re-weighted to the population. Odds ratios with 95% confidence intervals (OR, CI) from multivariate logistic regression were used to estimate associations of seroprevalence with interview data. KSHV seroprevalence was 8.…
Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30
Abstract Background To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV). Methods In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by li…