Risk Of Kaposi's Sarcoma Research Articles

Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma herpesvirus viremia in kidney allograft recipients.

Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease in immunocompromised patients including allograft recipients. Detection of KSHV DNA in blood, as well as host genetic polymorphisms has been found to be associated with an increased risk for KS. We investigated an association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi Arabia. In total, 152 KTR who have survived kidney transplantation for at least 6 months were included in the study. KSHV viremia was determined by real-time polymerase chain reaction (PCR). Genotyping of SNPs in the VEGFA region was performed by PCR and direct sequencing, as well as by restriction fragment length polymorphism. KSHV DNA was detected in 28.9% (n = 44) of the study population. The A-allele at position C172A VEGFA gene promoter region was found to be associated with KSHV viremia (odd ratio [OR] = 4.8, P = 0.005). In addition, the G-allele at position C+405G in the 5'-untranslated region was associated with KSHV viremia in women, but not in men (OR = 3.98, P = 0.004). Our results suggest an association of VEGFA polymorphisms with KSHV viremia among KTR in this study population. A limitation of our study is that the results can only be predicated for patients 6 months after kidney transplantation and should be validated in another cohort with larger sample size.

Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy

BackgroundHuman herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective. ObjectiveTo determine whether PI-based HAART regimens may more effectively inhibit HHV-8 shedding compared to regimens without PIs. Study designProspective, observational study of 142 HIV-1 and HHV-8 co-infected men conducted in Seattle, Washington. Quantitative HHV-8 PCR testing was performed on daily swabs of the oropharynx, the primary site of HHV-8 replication. Associations between antiretroviral regimen and detection of HHV-8 DNA in swabs were evaluated using generalized estimating equations. ResultsHHV-8 DNA was detected in 3016 (26%) of 11,608 specimens collected. PI-based HAART was associated with a statistically significantly lower frequency of detection (RR 0.2; 95% CI 0.1–0.5) compared to ART-naïve persons, whereas HAART without a PI was not (RR 0.7; 95% CI 0.4–1.3). Compared to ART-naïve persons, there was also a trend toward lower quantities of HHV-8 detected during treatment with HAART regimens that contained a PI. These associations between PIs and measures of HHV-8 shedding could not be attributed to use of nelfinavir, which inhibits HHV-8 replication in vitro, and were independent of CD4 count and HIV plasma viral load (VL). ConclusionsHAART regimens that contain PIs appear to decrease HHV-8 shedding compared to NNRTIs. Further study of PI-based HAART is warranted to determine the optimal regimens for prevention and treatment of KS.

Cancer burden among HIV-positive persons in Nigeria: preliminary findings from the Nigerian AIDS-cancer match study.

BackgroundAlthough Nigeria has a large HIV epidemic, the impact of HIV on cancer in Nigerians is unknown.MethodsWe conducted a registry linkage study using a probabilistic matching algorithm among a cohort of HIV positive persons registered at health facilities where the Institute of Human Virology Nigeria (IHVN) provides HIV prevention and treatment services. Their data was linked to data from 2009 to 2012 in the Abuja Cancer Registry. Match compatible files with first name, last name, sex, date of birth and unique HIV cohort identification numbers were provided by each registry and used for the linkage analysis. We describe demographic characteristics of the HIV clients and compute Standardized Incidence Ratios (SIRs) to evaluate the association of various cancers with HIV infection.ResultsBetween 2005 and 2012, 17,826 persons living with HIV (PLWA) were registered at IHVN. Their median age (Interquartile range (IQR)) was 33 (27–40) years; 41% (7246/17826) were men and 59% (10580/17826) were women. From 2009 to 2012, 2,029 clients with invasive cancers were registered at the Abuja Cancer Registry. The median age (IQR) of the cancer clients was 45 (35–68) years. Among PLWA, 39 cancer cases were identified, 69% (27/39) were incident cancers and 31% (12/39) were prevalent cancers. The SIR (95% CI) for the AIDS Defining Cancers were 5.7 (4.1, 7.2) and 2.0 (0.4, 3.5), for Kaposi Sarcoma and Cervical Cancer respectively.ConclusionThe risk of Kaposi Sarcoma but not Cervical Cancer or Non-Hodgkin’s Lymphoma, was significantly increased among HIV positive persons, compared to the general population in Nigeria.

British HIV Association guidelines for HIV‐associated malignancies 2014

<scp>B</scp>ritish <scp>HIV</scp> Association guidelines for <scp>HIV</scp>‐associated malignancies 2014

Risk of Kaposi Sarcoma Among Immigrants to Sweden

Kaposi sarcoma (KS) is a locally aggressive endothelial tumour that is classified into 4 clinico-epidemiological forms: classic KS affecting lower limbs in elderly Mediterranean or East European men; endemic KS occurring in extremities among Equatorial African middle-aged men and children; iatrogenic KS involving lower limbs in immunosuppressive patients; and AIDS-associated (epidemic) KS observed among homo- and bisexual HIV-1-infected young men (1, 2). The world-wide epidemiology of KS has changed by spreading of HIV infection (1). For example, KS represented 7% of all cancers in Sub-Saharan African men in the 1960s, whereas in the 1980s the rate increased to 50%. Furthermore, the age distribution of KS has changed from elderly (in classic form) to the late thirties (in epidemic form). KS is a rare tumour in Nordic countries; the incidence is 0.1-0.2/100,000 according to the Cancer Incidence in Five Continents (CI5) report (3). According to this source, the rate in many Asian countries is <0.5/100,000, whereas African American men have a rate of 6.2/100,000. The highest rate is in men from Zimbabwe (52.2/100,000) (3). Human herpesvirus 8 (HHV-8) is the recognised cause of all forms of KS (2). There is discrepancy between the prevalence of HHV-8 and KS incidence in some populations suggesting underreporting of KS or the existance of some unknown protective factors for KS (1). Migrant studies provide data on international differences in cancer rates (4). Furthermore, studies on immigrants may provide supplementary and confirmatory data on the incidence of cancer in countries without local cancer registries. A few available studies on immigrants have focused only on classic KS (5, 6). In the present study, we report mean age at diagnosis and KS rates by site in first-generation immigrants to Sweden. (Less)

Population-based assessment of kaposi sarcoma-associated herpesvirus DNA in plasma among Ugandans.

Risk of Kaposi sarcoma (KS) is linked to detection of Kaposi sarcoma-associated herpesvirus (KSHV) DNA in plasma, but little is known about the prevalence and risk factors for plasma KSHV DNA detection among the general population where KS is endemic. Correlates of KSHV plasma detection were investigated in a population-based sample of adult Ugandans (15-59 years) who participated in an HIV/AIDS serobehavioral survey in 2004/2005. KSHV DNA was measured in plasma of 1,080 KSHV seropositive and 356 KSHV seronegative persons using polymerase chain reaction (PCR). KSHV DNA in plasma was detected in 157 (8.7%) persons; of these 149 (95%) were KSHV seropositive and 8 (5%) were seronegative. Detection of KSHV DNA in plasma was significantly associated with male sex (P < 0.001), older age (P = 0.003), residence in a rural versus urban area (P = 0.002), geographic region (P = 0.02), and being KSHV seropositive (13.8% seropositive vs. 2.3% seronegative, P < 0.001). In a multivariable model, KSHV DNA plasma quantity was significantly higher in men (P = 0.002), inversely associated with age (P = 0.05), and residing in an urban area (P = 0.01). In Uganda, KSHV is detected more frequently in the plasma of adult males and residents of rural regions, potentially explaining the increased risk of KS in these subsets of the Ugandan population.

High seroprevalence of human herpesvirus type 8 in patients with end-stage renal disease in Taiwan

BackgroundHuman herpesvirus type 8 (HHV-8) is the aetiologic agent of Kaposi's sarcoma (KS). The incidence of KS in renal transplant patients is much higher than in healthy controls. The risk is even higher among recipients seropositive for HHV-8 before transplantation. Patients with end-stage renal disease (ESRD) are immunocompromised and are candidates for renal transplantation, but HHV-8 seroprevalence in ESRD patients has not been well documented. ObjectivesThis study aimed to evaluate HHV-8 seroprevalence in ESRD patients in a cohort in Taiwan. Study designBlood samples collected from 149 ESRD patients and 149 age- and sex-matched healthy controls were analysed for HHV-8 antibody with immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) and for HHV-8 DNA with polymerase chain reaction. ResultsSeropositivity and titres for HHV-8 antibodies with IFA as well as seropositivity with ELISA were significantly greater in ESRD patients than in healthy controls (P=0.006, 0.001 and 0.003, respectively). Patients with a history of taking herbal medicine had significantly greater ELISA positivity than those without such a history (P=0.004). ELISA positives, particularly patients, had much higher IFA antibody titres than ELISA negatives (P<0.0001). Seropositivity in ESRD patients was not related to lymphopaenia, monocytosis, dialysis duration or a history of transfusion. Two diabetic ESRD patients were positive for HHV-8 DNA. ConclusionsESRD patients had significantly greater HHV-8 seropositivity than healthy controls in Taiwan. This association seems to be related to the geographic location of the cohort and invites further studies for the early association of HHV-8 infection in ESRD patients and risk for KS.

Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution. : In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996-2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests. The risk of Kaposi sarcoma was very high during months 1-3 on cART (N = 160, RRCrude 3.94, 95% CI 3.26-4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02-1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% CI 1.42-2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41-0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/μl) or PJP (61 cells/μl) within 3 months than in those who did not develop these conditions (>250 cells/μl). Notably, median CD4 cell count change was +44 cells/μl per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/μl per month with incident PJP (P = 0.0003). Failure of CD4 cell count reconstitution during months 1-3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1-3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.

Incidence of Post Transplant Malignancies in Renal Transplant Recipients: Single Center Experience

The incidence of malignancy in transplant recipients is known to be higher than that in the general population. However, the types of malignancies vary geographically, and the relative risks for malignancy in transplant recipients are different, compared with that of the general population. We investigated the incidence and characteristics of malignancies after renal transplantation in a single center analysis. A total of 2740 renal recipients who underwent transplantation between June 1990 and Dec 2010 were enrolled in this retrospective study. During the follow-up period, 153 post-transplant malignancies were developed in 148 of 2740 patients. 24 of 148 patients were died from malignancy. The cumulative incidence of cancer at 1, 5, 10, 15, and 20 years was 0.58%, 3.1%, 7.2%, 13.2 %, and 25% respectively. The post-transplant malignancies were detected from 3 to 226 months after transplantation, with a mean duration of 78.1 ± 55.0 months. Post-transplant lymhoproliferative disorder (PTLD) [18 (11.7%)] was the most common malignancy. Risk of Kaposi sarcoma, PTLD, skin cancer, uterine cancer, urologic malignancy, biliary tract cancer, and breast cancer were more than 10-times higher in KT recipients than general population. In conclusion, the incidence of post transplant malignancy increased rapidly with laps of time following transplantation and related with duration of immunosuppressant exposure. A more vigorous cancer surveillance program should be adapted to detect early cancer in early stage especially in long term follow up patients.

Incidence and risk factors of AIDS-defining cancers in a cohort of HIV-positive adults: Importance of the definition of incident cases

BackgroundThe aim of this study was to investigate the incidence and risk factors for the development of AIDS-defining cancers (ADCs); and to investigate the effect of making different assumptions on the definition of incident cases. MethodsA multicentre cohort study was designed. Poisson regression was used to assess incidence and risk factors. To account for misclassification, incident cases were defined using lag-times of 0, 14 and 30 days after enrolment. ResultsA total of 6393 HIV-positive subjects were included in the study. The incidences of ADCs changed as the lag periods were varied from 0 to 30 days. Different risk factors emerged as the definition of incident cases was changed. For a lag time of 0, the risk of Kaposi sarcoma [KS] and non-Hodgkin lymphoma [NHL] increased at CD4 counts <200/ml. HAART was associated with lower risk of NHL and KS. Men who had sex with men had a higher risk of KS. KS and NHL were not associated with viral load, gender, or hepatitis B or C. The results were similar for a lag-time of 14 and 30 days; however, hepatitis C was significantly associated with NHL. ConclusionsThis analysis shows the importance of the definition of incident cases in cohort studies. Alternative definitions gave different incidence estimates, and may have implications for the analysis of risk factors.

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 regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA responses had current KS lesions, whereas five of six cases with KSHV-K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86-30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and KSHV-non-specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution.

Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults

Given the well documented occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients who recently started combination antiretroviral therapy (cART), we examined whether cART initiation increased the risk of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) using data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration. A nested matched case-control study design was used to assess the effects of individual CD4 cell trajectories and exposure to cART close to the time of cancer diagnosis. Cases were patients diagnosed with either cancer during follow-up with a minimum of two consecutive CD4 cell readings within the year preceding diagnosis. For each case, up to 10 controls, matched by sex and cohort, were selected by random sampling. Changes in CD4 cell count, calculated by simple and piecewise linear regression, and recent exposure to cART were compared within matched case-control sets using conditional logistic regression. Using data on 689 cases and 4588 controls, we found that an initially low and decreasing CD4 cell count during the year prior to cancer diagnosis is predictive of both Kaposi sarcoma and NHL. Most of this cancer risk is explained by the immunodeficiency characteristic of the period before cART initiation; however, an increased cancer risk was seen in patients who initiated cART in the previous 3 months (odds ratio 2.31; 95% confidence interval 1.33, 4.00). Although IRIS may transiently increase the risk of Kaposi sarcoma or NHL in HIV-infected patients, the timely initiation of cART remains the best strategy to avoid the development of these malignancies.

Association of haptoglobin phenotypes with the development of Kaposi’s sarcoma in HIV patients

Kaposi's sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein, exerts several immunomodulatory effects and is characterized by a genetic polymorphism leading to three major phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). This study investigated the influence of Hp genetic polymorphism on the development of KS in HIV-positive patients. 661 HIV patients were enrolled in the study with a median age of 35years and a median follow-up time of 57months. Hp phenotyping was performed using hemoglobin-supplemented starch gel electrophoresis. In case of low Hp concentration high pressure gel permeation chromatography (HPGPC) was used. The Hp 1-1 phenotype was associated with a significant higher risk of KS compared to the combined group of Hp 2-1 and Hp 2-2 patients (p<0.0005) which remained significant after adjustment for possible confounding variables (age, gender and AIDS status) (p<0.001). In contrast, the Hp 2-1 phenotype carried the lowest risk. These findings point to the involvement of Hp phenotypes in the pathogenesis of KS, which may be due to a difference in skin immunosurveillance between the Hp phenotypes.

Incidence of Kaposi sarcoma in HIV-infected patients receiving antiretroviral therapy: A prospective multicohort study from southern Africa.

1589 Background: The incidence of Kaposi sarcoma (KS) is high in Southern Africa: KS is the most common cancer in HIV-infected persons. Data on KS in patients receiving antiretroviral therapy (ART) are, however, scarce in Africa. Within the framework of a large multi-cohort project, the International epidemiologic Database to Evaluate AIDS (IeDEA), we studied the incidence and risk factors for the development of KS in HIV-infected patients starting ART in Southern Africa. Methods: We analyzed prospectively collected data of HIV-infected patients who started ART with three antiretroviral drugs from at least two classes. Prevalent KS cases diagnosed before or at start of ART were excluded. Incidence rates and 95% confidence intervals (CI) were calculated based on the Poisson distribution; risk factors were estimated using crude and adjusted Cox models. Hazard ratios (HR) with 95% CI and medians with interquartile ranges (IQR) are presented. Results: 185,924 patients from 7 cohort studies in Botswana, Mozambique, South Africa, Zambia, Zimbabwe with 376,630 person-years of follow-up were included. At start of ART median age was 34 years (IQR 28–41) and median CD4 cell count 145 cells/µl (IQR 73-225). 61% of patients were female. A total of 601 incident KS cases were recorded. The incidence for KS in patients on ART was 160 (95% CI 147-173) per 100,000 person-years. The risk for KS increased with age. Adjusting for age, gender, WHO stage and CD4 cell count adults >40 years had a more than ten-fold increased risk for developing KS compared to infants (HR 11.8, 95% CI 3.0-46.2); men were more likely to develop KS compared to women (HR 1.4, 95% CI 1.1-1.7) and the risk to develop KS was increased in patients with AIDS at start ART (WHO stage IV vs. I: HR 2.2, 95% CI 1.6-3.1). Conclusions: In Southern African countries with a high prevalence of HHV-8 the risk to develop KS in HIV infected patients receiving ART increases steeply with age and is higher in patients with more advanced HIV infection.

Malignancies after kidney transplantation: a 40-year single-center experience in Korea

Cancer is a well-recognized complication of kidney transplantation (KT), but nearly almost all data have come from Western countries. The aim of this study was to determine the incidence, type, and risk factors of malignancy after KT in Korea. The 1695 patients who underwent KT between 1969 and 2009 were studied retrospectively. Results were compared with a cohort of patients without cancer from the same center. During the follow-up period, 136 of 1695 patients developed 141 post-transplant malignancies (PTM). The cumulative incidence of cancer at 1, 5, 10, 20, and 30 years was 0.64%, 2.42%, 7.89%, 21.49%, and 66.35% respectively. Stomach cancer was the most common PTM. Risk of Kaposi sarcoma, malignant lymphoma, skin cancer, cervical cancer, and renal cell carcinoma was more than 10-times higher in KT recipients. Multivariate logistic regression analysis showed that cancers were clearly associated with recipients' age, recipients' gender, duration of graft function and follow-up period. Our data suggest that most malignancies develop more frequently after KT, but the incidence of individual cancer is different from Western countries. A more vigorous cancer surveillance program should be adapted to risk associated with transplant recipients, especially older, female or long-term follow-up recipients or those with functioning grafts.

Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi's sarcoma in Iran

Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8) infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%), renal transplant recipients (25%) and HIV (45.7%) patients compared to blood donors (2%). Kaposi's sarcoma (KS) is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.

Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily

BackgroundEcologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS).MethodsIn 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 exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with Ptrend ≤ 0.15 were retained in a backward elimination regression model.ResultsAdjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (ORadj) 0.96, 95% confidence interval (CI) 0.73 - 1.25, Ptrend = 0.87], nor was it related to any factor scores or cluster of plants (P = 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (Ptrend = 0.02 to 0.10) and with residential exposure to six soils (Ptrend = 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (ORadj 4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (ORadj 7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (ORadj 0.26 and 0.47, respectively, Ptrend = 0.05).ConclusionsKS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.

Kaposi sarcoma (KS)-associated herpesvirus microRNA sequence analysis and KS risk in a European AIDS-KS case control study.

We recently identified polymorphisms in Kaposi sarcoma-associated herpesvirus (KSHV)-encoded microRNA (miRNA) sequences from clinical subjects. Here, we examine whether any of these may contribute to KS risk in a European AIDS-KS case-control study. KSHV load in peripheral blood was determined by real-time quantitative polymerase chain reaction. Samples that had detectable viral loads were used to amplify the 2.8-kb miRNA encoding region plus a 646-bp fragment of the K12/T0.7 gene. Additionally, we characterized an 840-bp fragment of the K1 gene to determine KSHV subtypes. KSHV DNA was detected in peripheral blood mononuclear cells of 49.6% of case patients and 6.8% of controls, and viral loads tended to be higher in case patients. Sequences from the miRNA-encoding regions were conserved overall, but distinct polymorphisms were detected, some of which occurred in primary miRNAs, pre-miRNAs, or mature miRNAs. Patients with KS were more likely to have detectable viral loads than were controls without disease. Despite high conservation in KSHV miRNA-encoded sequences, polymorphisms were observed, including some that have been reported elsewhere. Some polymorphisms could affect mature miRNA processing and appear to be associated with KS risk.

Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma

Classic Kaposi sarcoma (KS) is exceedingly rare in children from the Mediterranean Basin, despite the high prevalence of human herpesvirus-8 (HHV-8) infection in this region. We hypothesized that rare single-gene inborn errors of immunity to HHV-8 may underlie classic KS in childhood. We investigated a child with no other unusually severe infectious or tumoral phenotype who died from disseminated KS at two years of age. Whole-exome sequencing in the patient revealed a homozygous splice-site mutation in STIM1, the gene encoding stromal interaction molecule 1, which regulates store-operated Ca(2+) entry. STIM1 mRNA splicing, protein production, and Ca(2+) influx were completely abolished in EBV-transformed B cell lines from the patient, but were rescued by the expression of wild-type STIM1. Based on the previous discovery of STIM1 deficiency in a single family with a severe T cell immunodeficiency and the much higher risk of KS in individuals with acquired T cell deficiencies, we conclude that STIM1 T cell deficiency precipitated the development of lethal KS in this child upon infection with HHV-8. Our report provides the first evidence that isolated classic KS in childhood may result from single-gene defects and provides proof-of-principle that whole-exome sequencing in single patients can decipher the genetic basis of rare inborn errors.