Epidemic Kaposi's Sarcoma Patients Research Articles

Unique circulating microRNA profiles in epidemic Kaposi's sarcoma.

BackgroundHuman herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS.MethodsThis was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data.ResultsFifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis.ConclusionsThis study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Admitted AIDS-associated Kaposi sarcoma patients: Indications for admission and predictors of mortality.

Kaposi sarcoma (KS) is an AIDS-defining angioproliferative malignancy associated with high morbidity and mortality. Most KS patients in regions with high incidence such as sub-Saharan Africa present late with advanced stage disease. Admitted KS patients have high mortality rates. Factors associated with mortality of admitted KS patients are poorly defined.We conducted a retrospective file review to ascertain reasons for admission and identify factors associated with mortality of admitted HIV-associated (epidemic) KS patients in Zambia. Baseline study variables were collected, and patients were retrospectively followed from admission to time of discharge or death.Mortality rate for admitted epidemic KS patients was high at 20%. The most common reasons for admission included advanced KS disease, severe anemia, respiratory tract infections, and sepsis. The majority (48%) of admitted patients had advanced clinical stage with visceral involvement on admission. Clinical predictors of mortality on univariate analysis included visceral KS [odds ratio (OR) = 13.74; 95% confidence interval (95% CI) = 1.68–113; P = 0.02), fever (OR = 26; 95% CI = 4.85–139; P = .001), and sepsis (OR = 35.56; 95% CI = 6.05–209; P = .001). Baseline hemoglobin levels (5.6 vs 8.2 g/dL; P = .001) and baseline platelet counts (63 x 10^9/L vs 205 x 10^9/L; P = .01) were significantly lower in mortalities vs discharges. Baseline white cell counts were higher in mortalities vs discharges (13.78 x 10^9/L vs 5.58 x 10^9/L; P = .01), and HIV-1 viral loads at the time of admission were higher in mortalities vs discharges (47,607 vs 40 copies/μL; P = .02). However, only sepsis (or signs and symptoms of sepsis) were independently associated with mortality after controlling for confounders.In conclusion, common reasons for admission of epidemic KS patients include advanced disease, severe anemia, respiratory tract infections, and signs and symptoms of sepsis. Signs and symptoms of sepsis are independent predictors of mortality in these patients.

Differential Immune Responses in Epidemic and Endemic Tanzanian Kaposi Sarcoma Patients

Background: Mechanisms underlying Kaposi sarcoma (KS) development are unclear. The high incidence of KS in HIV-1+ individuals implicates immune dysregulation in epidemic KS (EpKS) development. In African endemic KS (EnKS), the immune response is uncharacterized. Aim: The aim was to assess a comparative quantification between newly diagnosed Tanzanian EpKS and EnKS patients, and asymptomatic controls. We also report the first comparison of KSHV NAb prevalence and titer between EpKS and EnKS patients. Methods: To compare innate and adaptive immune responses, we recruited histologically confirmed Tanzanian EpKS and EnKS patients, as well as noncancer controls. After differential detection of KSHV nucleic acids in tissues, neutralizing antibody (NAb), levels of cytokines/chemokines, and T-cell differentiation subsets were quantified. The Mann-Whitney U-test was used to assess median differences between groups. All tests were 2-tailed and P-values < 0.05 were considered significant. Results: A total of 180 patients have been recruited in this study. In addition, a comparable 25 EpKS and 10 EnKS as well as 10 noncancer controls were recruited for this study. KSHV was significantly more frequently detected in EpKS patients than in EnKS. While all EpKS, and some EnKS patients mounted NAb responses, the EpKS patients had higher prevalence and titer of NAb compared with EnKS patients ( P = 0.001). Levels of the cytokines IP-10 and IL-10 were higher in EpKS vs EnKS patients ( P = 0.006 and P = 0.005 respectively), whereas, IL-4 was lower in EpKS vs EnKS patients ( P = 0.004). The levels of all 14 cytokines/chemokines measured were comparable between EnKS patients and HIV− controls ( P < .05 ). The distribution of CD4+ and CD8+ T-cells was similar between EpKS and EnKS such as naive and effector T-cells were depleted while central memory T-cells were elevated in both KS forms. Conclusion: The detection of similar abnormalities in T-cell differentiation subsets in both EpKS and EnKS as compared with controls, suggests that KSHV-induced T-cell dysfunction plays a major role in the disease, and that HIV-1 coinfection is only exacerbating and accelerating KSHV pathogenesis and KS development.

Immunological profile of endemic and epidemic Kaposi's sarcoma patients in Dar-es-Salaam, Tanzania.

Kaposi's sarcoma (KS) presents in four clinicopathological types namely classical/sporadic (CKS), endemic African (EKS), iatrogenic (IKS) and that associated with AIDS (AKS). Recently a putative herpes virus (HHV-8) was described and shown to be present in all four types of KS. The immunological status of patients with EKS has been conflicting. In this study total leucocyte counts, total lymphocyte counts and lymphocyte subsets of patients with EKS and AKS were determined by flow cytometry and compared to those of healthy HIV-1 seronegative controls. Results show that 50% of EKS lesions were of nodular type. Patients with EKS had significantly lower levels of CD4+ T- lymphocytes and CD4:CD8 ratio but significantly higher CD8+ T-lymphocytes compared to controls. Patients with AKS had significantly lower levels of CD4+ T-lymphocytes and also CD4:CD8 ratios but significantly higher percentage of CD8+ T-lymphocytes when compared with EKS patients. These findings indicate that in both forms of KS there is a certain degree of immunological disturbance which is more conspicuous in AKS because of HIV infection and suggests that HIV-1 acts synergistically with the aetiological agent (HHV-8) to cause a more aggressive type of KS.

The absence of Tat sequences in tissues of HIV-negative patients with epidemic Kaposi's sarcoma.

Tat, an essential regulatory protein of HIV, acts as a growth factor for Kaposi's sarcoma (KS)-derived cells in culture. We tested the hypothesis that HIV-negative epidemic KS patients who are also at high risk for HIV disease might have been infected with a defective HIV-1 virus that retained the ability to express Tat. We evaluated the presence of Tat sequences in KS tissue and peripheral blood mononuclear cells (PBMC) of HIV-1-negative individuals with epidemic KS who had risk factors for HIV infection by polymerase chain reaction using specific primers for the Tat region of HIV-1. No evidence for the presence of Tat-1 sequences or for Tat-expressing defective HIV-1 virus was found. These results suggest that HIV-1 Tat does not play a role in the initiation of KS in HIV-1-negative individuals. Tat might play an indirect role in epidemic KS in HIV-infected patients.

Nutritional factors in epidemic Kaposi's sarcoma.

The role of nutritional factors in the management of acquired immunodeficiency syndrome-related, or epidemic, Kaposi's sarcoma (EKS) is complex, since there are known interactions between malnutrition, immunodeficiency, and cancer. Malnutrition is a well-established cause of immune aberrations, which are seen in deficiencies of both protein and energy, as well as specific nutrients, particularly trace metals. Conversely, malnutrition is a common result of both cancer and immunodeficiency. Cancer patients without an obviously immunological pathogenesis frequently have malnutrition and cachexia, mainly as a result of a decreased dietary intake and poorly defined host-tumor interactions (commonly labeled "hypermetabolic"). Patients with primary immunodeficiency syndromes similarly experience a triad of diarrhea, malabsorption, and weight loss, which are responsible for the development of malnutrition. This triad is common in patients with AIDS, with or without the presence of Kaposi's sarcoma. The specific mechanisms of these interactions in EKS patients are largely unexplored; although some can be explained by the enteropathic effects of opportunistic infections, others can not. Some investigators have advocated careful nutritional evaluation of all AIDS patients, with vigorous nutritional support to be provided where assessment reveals suboptimal nutritional status. Specific nutrient deficiencies have been reported, of which selenium may be the most interesting; preliminary data indicate that it may be responsible for a malnutrition-related immunodepression seen with AIDS. Such supportive measures may significantly improve symptomatic relief, but there is as yet no evidence that they alter the course of the disease.