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ABSTRACT Background: The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. Objectives: To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoid-proliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. Methods: HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. Results: We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. Conclusion: IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.
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Background: The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. Objectives: To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. Materials and Methods: HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. Results: We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. Conclusion: IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.
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Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.
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Infecções por HIV , Sarcoma de Kaposi , Sulfonamidas , Humanos , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/metabolismo , Infecções por HIV/metabolismo , Valganciclovir/metabolismo , Valganciclovir/uso terapêutico , Linfócitos T CD4-Positivos/metabolismo , Subpopulações de Linfócitos T , Linfócitos T CD8-Positivos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Carga ViralRESUMO
Human herpesvirus-8 infection (HHV-8) is the causative agent of Kaposi sarcoma (KS) and is highly prevalent among people living with HIV (KS/HIV). It has been reported that valganciclovir (VGC) reduces HHV-8 replication in KS/HIV patients. However, currently it is unclear if VGC modifies the frequency and induces changes in markers of immune regulation of immune cells necessary to eliminate HHV8-infected cells, such as Natural Killer (NK) and NK T cells (NKT). This study evaluated the effect of VGC used as antiviral HHV8 therapy in KS patients on the frequency of NK and NKT subpopulations based on the CD27 and CD57 expression, and the immunosenescence markers, PD-1 and KLRG1. Twenty KS/HIV patients were followed-up at baseline (W0), 4 (W4), and 12 weeks (W12) of the study protocol. Among them, 10 patients received a conventional treatment scheme (CT), solely antiretroviral therapy (ART), and 10 patients received a modified treatment regime (MT), including VGC plus ART. In both groups, bleomycin/vincristine was administrated according to the treating physician's decision. The soluble levels of IL-15, PD-L1, PD-L2, and E-cadherin were quantified across the follow-up. Our results showed that the higher IL-15 levels and lower NK frequencies cells in KS/HIV patients reach almost normal values with both treatments regimes at W12. CD27+ NK and NKT cell frequencies increased since W4 on KS/HIV patients with MT. Furthermore, PD-1 expression decreased while KLRG1 increased on NK and NKT subpopulations at W12, and it is accompanied by increased PD-L1 plasma level since W4. Our study highlights the disruption of NK and NKT subpopulations in patients with KS/HIV and explores VGC treatment's contribution to immune reconstitution during the first weeks of treatment.
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The aim of this article was to evaluate the clinical and laboratory profile of people with oral Kaposi's sarcoma (KS) associated with AIDS (KS-AIDS), followed-up at a public university hospital in Salvador, Bahia, Brazil, in the past 10 years. We identified patients diagnosed with KS-AIDS, presenting oral manifestation from January 2007 to December 2017. We searched, in the hospital information systems, the patient demographics, diagnostic data, treatment, image studies, and oral photographic records. Of the 39 cases of KS-AIDS identified at the institution, 14 (22.8%) presented oral lesions. There was a predominance of black men, with a mean age of 32.5 years. Most cases (85.1%) manifested signs of KS simultaneously with the diagnosis of HIV infection, with extremely low initial CD4 T cell counts (average of 52.6 cells/mm2) and visceral involvement (64.3%). The palate (32.1%) and gingiva (21.4%) were the most affected oral sites. Histologically, the tumors exhibited proliferation of spindle cells between vascular clefts and extravasated erythrocytes. Oral KS-AIDS was frequent in young black adult men, with severe immunosuppression and high viral load counting, mostly with lesions manifested in the same period of diagnosis of infection by the HIV.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Sarcoma de Kaposi , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Infecções por HIV/complicações , Humanos , Laboratórios , Masculino , Carga ViralRESUMO
El cáncer es una causa importante de morbilidad y mortalidad en los receptores de trasplante. La combinación de infecciones virales, terapia de inmunosupresión y la alteración en el sistema inmune en los pacientes trasplantados, contribuyen al desarrollo de cáncer. El sarcoma de Kaposi es causado por el virus herpes humano 8 (VHH-8), y aunque es raro en la población general, puede ser hasta 300 veces más frecuente en los pacientes con trasplante renal. El diagnóstico de la enfermedad se realiza a menudo con base en las características de las lesiones, pero debe ser confirmado por histología. En años recientes, los inhibidores de mTOR han mostrado ser efectivos para el control del sarcoma de Kaposi en los pacientes trasplantados, ya que se interrumpe el efecto antiapoptótico y la angiogénesis dependientes de la proteína mTOR, los cuales son esenciales para el desarrollo y la propagación de células malignas. Se presentan dos casos de pacientes con sarcoma de Kaposi ganglionar, sin lesiones en piel, en nuestro centro de trasplante, quienes respondieron de manera positiva al cambio del esquema inmunosupresor con inhibidores de mTOR
Cancer is a major cause of morbidity and mortality in transplant recipients. The combination of viral infections, immunosuppression therapy and immune system dysfunction in transplant patients contribute to the development of cancer. Kaposi sarcoma is caused by human herpes virus 8 (HHV-8) and although rare in the general population, it is reported to be up to 300 times more common in kidney transplant patients. Diagnosis of the disease is often made on the basis of the characteristic appearance of lesions, but must be confirmed by histology. In recent years, mTOR inhibitors have been shown to be effective in controlling Kaposi sarcoma in transplant patients, due to disruption of the antiapoptotic effect and angiogenesis dependent on the mTOR protein, which are essential for development and propagation of malignant cells. We present two case reports of patients with Kaposi sarcoma in lymph nodes and no skin lesions, who responded well to the immunosuppressive therapy switch with mTOR inhibitors
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Humanos , Sarcoma de Kaposi , Transplante de Rim , Herpesvirus Humano 8 , Serina-Treonina Quinases TOR , LinfonodosRESUMO
Kaposi sarcoma is an uncommon tumor that primarily arises in the skin and mucosal surfaces, but may metastasize to the internal organs. Four main variants of Kaposi sarcoma are recognized as the following: classic Kaposi sarcoma, which occurs in middle-aged or elderly men; epidemic Kaposi sarcoma, associated with human immunodeficiency virus infection; iatrogenic Kaposi sarcoma seen in patients on immunosuppressive drug therapy; and endemic Kaposi sarcoma. This report is of a case of classic Kaposi sarcoma in 55-year-old immunocompetent and human immunodeficiency virus-negative Dominican man who had lived in the United States for 2 years, who presented with a 2-year history of skin lesions on his lower extremities and soft palate. Biopsy of the soft palate was consistent with Kaposi sarcoma. The patient was treated with paclitaxel with a good response. This case report demonstrates the importance of recognizing that classic Kaposi sarcoma, first described almost 150 years ago, can still present in immunocompetent middle-aged men of all ethnicities.
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El sarcoma de Kaposi se ha convertido en uno de los tumores más prevalentes en África tras la epidemia de VIH, que afecta de una manera similar a hombres y mujeres. El retraso diagnóstico y el limitado acceso a tratamiento antirretroviral o quimioterapia condicionan el pronóstico de los pacientes que lo padecen. En este artículo se realiza una revisión sobre la referida enfermedad, con el objetivo de describir sus aspectos más relevantes en los últimos años en África, como son su epidemiología, caractéristicas clínicas y opciones terapéuticas existentes. Este tumor es provocado por la infección por virus herpes humano tipo 8, que resulta más prevalente en las zonas rurales del continente africano. Se postula la transmisión a través de la saliva como la vía más importante de contagio en África. La inmunodepresión que causa el VIH favorece el efecto oncogénico del virus. La forma epidémica de SK se manifiesta inicialmente como lesiones hiperpigmentadas o violáceas en la piel, que pueden extenderse a linfáticos o mucosas y a nivel sistémico, principalmente a pulmón o aparato digestivo. El síndrome de reconstitución inmune sistémica puede complicar la evolución del paciente. El inicio temprano de la terapia antirretroviral resulta imprescindible. Además, el pronóstico de los pacientes mejora con la suma de tratamiento quimioterápico con doxorrubicina, vincristina, etopóxido o bleomicina principalmente(AU)
Kaposi sarcoma (KS) has become one of the most prevalent tumors in Africa after the HIV epidemic. KS affects both men and women. Diagnostic delay and limited access to antiretroviral treatment or chemotherapy have an impact on the prognosis of KS patients. A review was conducted about KS with the purpose of describing its most outstanding characteristics in recent years in Africa, such as its epidemiology, clinical features, and existing therapeutic options. This tumor is caused by infection with human herpesvirus 8, which is more prevalent in rural areas of the African continent. Transmission via saliva was found to be the most important transmission route in Africa. HIV-related immunosuppression fosters the oncogenic effect of the virus. The epidemic form of KS initially presents as hyperpigmented or violet-colored skin lesions which may extend to lymph nodes or mucosae, or systemically, mainly to the lungs or the digestive tract. Systemic immune reconstitution syndrome may complicate the patient's evolution. Early start of antiretroviral therapy is indispensable. Additionally, prognosis improves with chemotherapy with doxorubicin, vincristine, etoposide or bleomycin, mainly(AU)
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Humanos , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/epidemiologia , Neoplasias Cutâneas/complicações , África Subsaariana/epidemiologia , Herpesvirus Humano 8/patogenicidade , Terapia Antirretroviral de Alta Atividade/métodosRESUMO
BACKGROUND: Mannose-binding lectin (MBL) plays an important role in the innate immune response by activating the complement system via the lectin pathway, and it has been studied in several viral infections; however, the influence of MBL in PLWHA infected with HHV-8 is unknown. The objective of this study was to verify the association of MBL deficient plasma concentrations in HIV/HHV-8 coinfected and HIV monoinfected patients and to correlate these concentrations with HIV viral load and CD4 counts in both groups. RESULTS: This was an analytical study of case-controls consisting of PLWHA monitored at the medical outpatient of Infectious and Parasitic Diseases of the clinical hospital in the Federal University of Pernambuco. Plasma concentrations of MBL were obtained by an enzyme-linked immunosorbent assay (ELISA) using a commercial Human Mannose Binding Lectin kit (MyBioSource, Inc.) that was performed according to the manufacturer's guidelines, with values < 100 ng/ml considered deficient. A total of 245 PLWHA samples were analysed; 118 were HIV/HHV-8 coinfected and 127 were HIV monoinfected; 5.1% (6/118) of the coinfected patients and 3.2% (4/127) of the monoinfected patients (p = 0.445) were considered plasma concentration deficient. The median of the plasma concentrations of MBL in the coinfected patients was 2803 log10 ng/ml and was 2.959 log10 ng/ml in the monoinfected patients (p = 0.001). There was an inverse correlation between the plasma concentrations of MBL and the HIV viral load in both groups, but no correlation with the CD4 count. CONCLUSIONS: Although the plasma concentrations considered deficient in MBL were not associated with HHV-8 infection in PLWHA, the coinfected patients showed lower MBL concentrations and an inverse correlation with HIV viral load, suggesting that there may be consumption and reduction of MBL due to opsonization of HIV and HHV-8, leading to the reduction of plasma MBL and non-accumulation in the circulation.
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Coinfecção , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1 , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8 , Lectina de Ligação a Manose/sangue , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , HIV-1/imunologia , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/imunologia , Herpesvirus Humano 8/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Carga ViralRESUMO
BACKGROUND: Kaposi's sarcoma (KS) is the most prevalent malignant neoplasia in human immunodeficiency virus positive (HIV+) patients for which the primary mode of management was chemotherapy. METHODS: We have presented the case of a newly diagnosed HIV+ male patient who was diagnosed with a pedunculated nodule in the anterior region of the hard palate, measuring 3.5 cm in diameter and with 2 months of evolution. RESULTS: Histopathological examination confirmed the clinical hypothesis of KS. Soon after the diagnosis, the patient started using combined antiretroviral therapy (Biovir and Kaletra), presenting a significant reduction of the lesion after 4 weeks. With 1.5 cm in diameter, the lesion was surgically removed. The patient was followed-up for 10 years without any recurrence. CONCLUSION: In antiretroviral-naive patients with a well-preserved immune system, the use of cART may be efficient in reducing the progression of the KS lesions, thus avoiding the use of chemotherapeutic agents.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Ritonavir/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Zidovudina/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Combinação de Medicamentos , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologiaRESUMO
BACKGROUND: Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients. RESULTS: A cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard® Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI = 1.2-7.6) of their last CD4 cell count being below 350 cells/mm3. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO. CONCLUSIONS: Host genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.
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Infecções por Herpesviridae/genética , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por HIV/virologia , Haplótipos , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8 , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Carga ViralRESUMO
Abstract: Background: Kaposi's sarcoma (KS) is a rare neoplasm with indolent progression. Since 1981, the Kaposi's sarcoma epidemic has increased as co-infection with HIV. Objectives: The study aimed to identify the clinical and demographic characteristics and therapeutic approaches in HIV/AIDS patients in a regional referral hospital. Methods: We analyzed the medical records of 51 patients with histopathological diagnosis of Kaposi's sarcoma hospitalized at Hospital Universitário João de Barros Barreto (HUJBB) from 2004 to 2015. Results: The study sample consisted of individuals 15 to 44 years of age (80.4%), male (80.4%), single (86.3%), and residing in Greater Metropolitan Belém, Pará State, Brazil. The primary skin lesions identified at diagnosis were violaceous macules (45%) and violaceous papules (25%). Visceral involvement was seen in 62.7%, mainly affecting the stomach (75%). The most frequent treatment regimen was 2 NRTI + NNRTI, and 60.8% were referred to chemotherapy. Study limitations: We assumed that more patients had been admitted to hospital without histopathological confirmation or with pathology reports from other services, so that the current study probably underestimated the number of KS cases. Conclusion: Although the cutaneous manifestations in most of these patients were non-exuberant skin lesions like macules and papules, many already showed visceral involvement. Meticulous screening of these patients is thus mandatory, even if the skin lesions are subtle and localized.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Sarcoma de Kaposi/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/tratamento farmacológico , Fatores Socioeconômicos , Brasil/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Centros de Atenção TerciáriaRESUMO
AIM: Saliva can play an important role in human herpesvirus-8 (HHV-8) transmission in endemic regions for Kaposi's sarcoma (KS). Little is known about HHV-8 oral shedding in immunocompetent individuals from non-endemic regions for KS. METHODS: We conducted a prospective study of HHV-8 salivary excretion among 59 healthy, immunocompetent individuals from São Paulo, Brazil, followed up weekly for 4 months, resulting in 16 saliva samples from each participant. Antibodies to HHV-8 latency-associated nuclear antigen (LANA) and lytic-phase antigens were investigated with immunofluorescence assays (IFA). HHV-8 DNA detection was performed using real-time polymerase chain reaction (PCR). RESULTS: All 59 individuals were seronegative to LANA and lytic antibodies. HHV-8 DNA was undetectable in saliva samples in 100% of the participants, totaling 944 samples and being consistently negative during the different periods of sampling, which lasted approximately 120 days. No sequences of HHV-8 DNA were detected in the saliva samples of healthy, immunocompetent adults by using real-time PCR, with the resulting data being consistent with IFA-based serological tests. CONCLUSIONS: Unlike other herpesviruses, HHV-8 is not excreted in the saliva of healthy individuals from non-endemic regions for KS.
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Herpesvirus Humano 8/isolamento & purificação , Herpesvirus Humano 8/patogenicidade , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/virologia , Actinas/metabolismo , Adulto , Anticorpos Antivirais , Antígenos Nucleares/genética , Antígenos Nucleares/imunologia , Antígenos Virais/genética , Antígenos Virais/imunologia , Brasil/epidemiologia , DNA Viral/isolamento & purificação , Feminino , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Projetos Piloto , Estudos Prospectivos , Saliva/virologia , Testes Sorológicos , Proteínas Virais/genética , Proteínas Virais/imunologia , Adulto JovemRESUMO
BACKGROUND: Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. METHODS: HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). RESULTS: Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. CONCLUSIONS: We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc.
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Citocinas/sangue , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 8 , Antígeno Prostático Específico/sangue , Idoso , Biomarcadores/sangue , Infecções por Herpesviridae/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Trinidad e Tobago/epidemiologiaRESUMO
OBJECTIVES: To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer. METHODS: The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsy-confirmed prostate cancer (n = 79) were compared with control participants (n = 87). RESULTS: Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men. CONCLUSIONS: These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer.
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Infecções por Herpesviridae/imunologia , Herpesvirus Humano 8/imunologia , Neoplasias da Próstata/imunologia , Células Th2/imunologia , Microambiente Tumoral/imunologia , Idoso , Estudos de Casos e Controles , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Interleucina-10/sangue , Interleucina-12/sangue , Interleucina-13/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Próstata/imunologia , Próstata/virologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/virologia , Trinidad e TobagoRESUMO
This cross-sectional study aimed to estimate the seroprevalence and risk factors for Human herpesvirus 8 (HHV-8) infection among people living with HIV/AIDS in Recife, Pernambuco, Brazil. A total of 500 individuals were tested for antibodies against HHV-8 using the whole-virus ELISA. The prevalence of anti-HHV-8 was 28.6% and the frequency among 140 men who have sex with men (MSM) was 38.6%. In the univariate model, there were significant associations with male gender, detectable HIV load, travel abroad, bissexual, and homossexual orientation. The first HHV-8 seroepidemiologic study, in northeast Brazil, documents a highly prevalent HHV-8 infection among MSM living with HIV/AIDS. J. Med. Virol. 88:2016-2020, 2016. © 2016 Wiley Periodicals, Inc.
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Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por HIV/epidemiologia , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8 , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Anticorpos Antivirais/sangue , Bissexualidade , Brasil/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/isolamento & purificação , Infecções por Herpesviridae/imunologia , Herpesvirus Humano 8/imunologia , Herpesvirus Humano 8/isolamento & purificação , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Viagem , Carga Viral , Adulto JovemRESUMO
BACKGROUND: The Caribbean island of Tobago, which is 97% African ancestry, has one of the highest rates of prostate cancer in the world. We have previously reported that human herpesvirus 8 (HHV-8) infection is significantly associated with prostate cancer in Tobago. In this study, we extend those results testing the hypothesis that HHV-8 seropositive Tobagonian men have a chronic HHV-8 infection in their prostates that is associated with increased inflammation. METHODS: Prostate sections were screened by immunohistochemistry for the expression of HHV-8 proteins K8.1 and LANA-1 and for presence of B cells (CD20) and macrophages (CD68). RESULTS: HHV-8 antigen expression representing lytic and latent infections was seen in 73.9% of prostates from HHV-8 seropositive subjects. Latent infections were seen predominantly in glandular epithelia whereas lytic gene expression was seen mainly in macrophages in prostate stroma. Macrophage infiltrates were significantly increased in sections expressing HHV-8 proteins. CONCLUSION: HHV-8 establishes a chronic latent infection in the prostate, which is associated with an increased macrophage infiltrate.
Assuntos
Infecções por Herpesviridae/patologia , Macrófagos/patologia , Próstata/patologia , Neoplasias da Próstata/virologia , Antígenos CD/metabolismo , Antígenos CD20/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos Virais/metabolismo , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores/metabolismo , Glicoproteínas/metabolismo , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8 , Humanos , Macrófagos/metabolismo , Masculino , Proteínas Nucleares/metabolismo , Próstata/metabolismo , Próstata/virologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Trinidad e Tobago , Proteínas Virais/metabolismoRESUMO
Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to <22.9% in healthier women and men. To understand HHV-8 transmission, we examined HHV-8 seroconversion and seroreversion, and risk factors for these changes in Tobago men. Serum specimens from a sub-cohort of Tobago Prostate Survey men, aged 40-81 years (n = 381/442), were collected at baseline and a subsequent visit between 3 and 9 years and tested for HHV-8 seropositivity using an immunofluorescence assay for antibodies against HHV-8 lytic antigens. Poisson distribution was used to calculate HHV-8 seroconversion and seroreversion rates and their 95% confidence intervals. Differences in baseline characteristics between HHV-seroconverters versus persistent HHV-8 seronegative men and HHV-8 seroreverters versus HHV-8 seropositive men were examined. HHV-8 seropositivity was 12.3% (N = 381) at baseline, with HHV-8 seropositivity significantly higher in increasing age groups, 40-49 (4.0%) to 70-81 (37.5%) years (P-value trend <0.0001). HHV-8 seroconversion and seroreversion rates were 0.23 per 100 person-years (95% C.I., 0.06-0.58) and 2.42 per 100 person-years (95% C.I., 0.89-5.26), respectively. There were significantly more HHV-8 seroconverters who reported "ever smoked cigarettes of >6 months" at baseline compared to HHV-8 persistent seronegative men (P-value = 0.03). Baseline characteristics of HHV-8 seroreverters did not differ from persistent seropositive men. Low HHV-8 seroconversion and seroreversion rates were found. Data suggest that HHV-8 transmission occurred at earlier ages, <40 years, in Tobago men.