0000000000181292
AUTHOR
James J. Goedert
Prevalence of Toscana and Sicilian Phlebovirus Antibodies in Classic Kaposi Sarcoma Case Patients and Control Subjects in Sicily
To assess whether arthropod bites promote Kaposi sarcoma (KS), we determined the seroprevalence of Sicilian (SFSV) and Toscana (TOSV) phlebovirus antibodies in 30 patients with classic KS and 100 controls in Sicily. Nine (6.9%) subjects, all controls, were positive for SFSV, whereas 41 (31.5%) were positive for TOSV. Seroprevalence with immunoglobulin (Ig) M or IgG against either virus was significantly higher in controls (43% vs 13.3% in case patients; P < .01). Adjusted for age, IgG seroprevalence was significantly lower in KS patients compared to controls (adjusted odds ratio, 0.22; 95% confidence interval, .07–.72). Low phlebovirus seroprevalence in patients with KS may reflect incapaci…
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…
Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls
Background: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. Methods: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. Results: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), where…
Immunoglobulin M seropositivity for Toscana virus in a random population sample in Sicily.
Summary Objectives High Toscana virus (TOSV) antibody seropositivity rates have been documented in the last decade, especially in the Mediterranean area. It is unclear if these rates are associated with a recent or past exposure to the virus. This is of importance, as primary infection can cause neurologic complications, especially in adults. The aim of the present study was to assess the current active TOSV circulation in western Sicily. Methods A cross-sectional seroprevalence study was conducted on 271 individuals aged 4–92 years, sampled from the general population of a small city. Each participant completed a self-administered questionnaire and provided serum, which was analyzed for th…
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…
Infection with human herpes virus type 8 in an area at high prevalence for hepatitis C virus infection in southern Italy
Summary. The Campania Region is a geographical area of southern Italy characterized by high incidence rates of hepatocellular carcinoma and of classic Kaposi's sarcoma. Epidemiological investigations carried out among different population groups in this region have found high prevalence rates of both hepatitis C virus (HCV) and human herpesvirus type 8 (HHV-8). To assess co-infection rates of HCV and HHV-8, we carried out a cross-sectional seroepidemiological study prevalence in Pomigliano d'Arco, a Health District of Campania located 20 km away from Naples. The overall rate of HCV/HHV-8 co-infection was 3.1%, 3.5% among men and 2.7% among women. No difference emerged in the HCV/HHV-8 co-i…
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.…
Seroprevalence of and risk factors for Toscana and Sicilian virus infection in a sample population of Sicily (Italy).
Summary Objective The present study aimed to assess seroprevalence of and risk factors for Toscana (TOSV) and Sicilian (SFSV) virus infections in a sample of Sicilian subjects. Methods A cross-sectional seroepidemiological study was conducted on 271 individuals. Each participant completed a self-administrated questionnaire and provided a serum sample which was analyzed for the presence of IgG specific anti-TOSV and anti-SFSV viruses. Results Overall, 90 subjects (33.2%) were positive for TOSV IgG, 25 (9.2%) were positive for SFSV IgG and 11 (4%) were positive for both the viruses. A higher risk for TOSV seropositivity was found in participants who were older (adjOR = 1.02 per year; 95% CI =…
Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non-specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily
Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non-specifically and specifically against the KS-associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV-seronegative controls were tested for interferon-γ T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV-latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regress…
Antibodies to human herpes virus type 8 (HHV8) in general population and in individuals at risk for sexually transmitted diseases in Western Sicily.
Human herpes virus 8 (HHV8) appears to be the primary aetiologic agent of Kaposi sarcoma (KS). To study the distribution of HHV8, a seroepidemiological study was carried out in western Sicily, where a high incidence rate of classical KS is well documented.A total of 970 sera of healthy human immunodeficiency virus (HIV) negative individuals of general population (1-70 years old) and 742 sera of individuals in different risk groups for HIV infection were evaluated by means of an indirect immunofluorescence assay able to detect antibodies to lytic and latent HHV8 antigens.Crude seroprevalence to HHV8 antigens was 11.5% in the general population, and it increased significantly with age from 6%…
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…