RESUMEN
Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.
Asunto(s)
Retrovirus Endógenos , Herpesvirus Humano 4 , Leucocitos Mononucleares , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/virología , Retrovirus Endógenos/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/genética , Adulto , Femenino , Masculino , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Leucocitos Mononucleares/metabolismo , Perfilación de la Expresión Génica , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/genética , Persona de Mediana Edad , Linfocitos B/inmunología , Linfocitos B/virología , Estudios de Casos y Controles , Linfocitos T/inmunología , Citocinas/metabolismo , Citocinas/genéticaRESUMEN
Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-É£, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.
Asunto(s)
Coinfección , Citocinas , Infecciones por Virus de Epstein-Barr , Infecciones por VIH , VIH-1 , Herpesvirus Humano 4 , Polimorfismo de Nucleótido Simple , Humanos , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Infecciones por VIH/complicaciones , Brasil/epidemiología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Masculino , Adulto , Femenino , VIH-1/inmunología , VIH-1/genética , Citocinas/genética , Citocinas/sangre , Persona de Mediana Edad , Coinfección/virología , Coinfección/inmunología , Coinfección/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/genética , Genotipo , Linfocitos T CD8-positivos/inmunología , Adulto Joven , Recuento de Linfocito CD4 , InmunogenéticaRESUMEN
Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with ß-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.
Asunto(s)
Citocinas , Citomegalovirus , Rechazo de Injerto , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Trasplante de Riñón , Trasplante de Hígado , Humanos , Trasplante de Riñón/efectos adversos , Citocinas/sangre , Citocinas/metabolismo , Niño , Herpesvirus Humano 6/inmunología , Masculino , Femenino , Preescolar , Trasplante de Hígado/efectos adversos , Citomegalovirus/inmunología , Rechazo de Injerto/virología , Rechazo de Injerto/inmunología , Herpesvirus Humano 4/inmunología , Adolescente , Lactante , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/inmunología , Receptores de Trasplantes , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/inmunología , HerpesviridaeRESUMEN
Epstein-Barr virus (EBV) is an gamma of herpes virus affecting exclusively humans, was the first oncogenic virus described and is associated with over seven different cancers. Curiously, the exchange of genes during viral infections has enabled the evolution of other cellular organisms, favoring new functions and the survival of the host. EBV has been co-evolving with mammals for hundreds of millions of years, and more than 95% of adults have been infected in one moment of their life. The infection is acquired primarily during childhood, in most cases as an asymptomatic infection. However, during adolescence or young adulthood, around 10 to 30% develop infectious mononucleosis. The NK and CD8+ T cells are the cytotoxic cells of the immune system that focus on antiviral responses. Importantly, an essential role of NK and CD8+ T cells has been demonstrated during the control and elimination of EBV-infected cells. Nonetheless, when the cytotoxic function of these cells is compromised, the infection increases the risk of developing lymphoproliferative diseases and cancer, often fatal. In this review, we delineate EBV infection and the importance of cytotoxic responses by NK and CD8+ T cells during the control and elimination of EBV-infected cells. Furthermore, we briefly discuss the main inborn errors of immunity that compromise cytotoxic responses by NK and CD8+ T cells, and how this scenario affects the antiviral response during EBV infection. Finally, we conclude the review by underlying the need for an effective EBV vaccine capable of preventing infection and the consequent development of malignancies and autoimmune diseases.
El virus Epstein-Barr es una variante del herpes virus que afecta exclusivamente a humanos; fue el primer virus oncogénico descrito y se ha relacionado con más de siete diferentes tipos de cáncer. Curiosamente, el intercambio de genes debido a infecciones virales ha permitido la evolución de los organismos celulares, favoreciendo el desarrollo de nuevas funciones y supervivencia del hospedero. El virus Epstein-Barr comparte cientos de millones de años de coevolución con la especie humana y más del 95% de la población adulta mundial se ha infectado en algún momento de su vida. La infección se adquiere principalmente durante la infancia, y en la mayoría de los casos aparece sin ninguna manifestación grave aparente. Sin embargo, en los adolescentes y la población joven-adulta, alrededor de un 10 a 30% evolucionan a mononucleosis infecciosa. Las células NK y T CD8+ son células citotóxicas cruciales durante las respuestas antivirales y se ha demostrado que que controlan y eliminan la infección por el virus Epstein-Barr. No obstante, cuando se afecta su función efectora, el desenlace puede ser fatal. El objetivo de esta revisión es describir la infección por el virus Epstein-Barr y el papel decisivo de las células NK y T CD8+ durante el control y eliminación de la infección. Además, se discuten brevemente los principales defectos genéticos que afectan a estas células y conllevan a la incapacidad para eliminar el virus. Finalmente, se resalta la necesidad de elaborar una vacuna efectiva contra el virus Epstein-Barr y cómo podrían evitarse los procesos neoplásicos y enfermedades autoinmunes.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Células Asesinas Naturales , Humanos , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Células Asesinas Naturales/inmunología , Linfocitos T CD8-positivos/inmunologíaRESUMEN
BACKGROUND: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein-Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. MATERIALS AND METHODS: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. RESULTS: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. CONCLUSIONS: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed.
Asunto(s)
Infecciones por Virus de Epstein-Barr/virología , Infecciones por VIH/inmunología , VIH-1/inmunología , Herpesvirus Humano 4/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Coinfección , Estudios Transversales , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/patología , Femenino , Genotipo , Infecciones por VIH/virología , Seropositividad para VIH , Herpesvirus Humano 4/inmunología , Humanos , Inmunidad , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
The Epstein-Barr virus (EBV) is a well-adapted human virus, and its infection is exclusive to our species, generally beginning in the childhood and then persisting throughout the life of most of the affected adults. Although this infection generally remains asymptomatic, EBV can trigger life-threatening conditions under unclear circumstances. The EBV lifecycle is characterized by interactions with other viruses or bacteria, which increases the probability of awakening its pathobiont capacity. For instance, EBV infects B cells with the potential to alter the germinal center reaction (GCR)-an adaptive immune structure wherein mutagenic-driven processes take place. HIV- and Plasmodium falciparum-induced B cell hyperactivation also feeds the GCR. These agents, along with the B cell tropic KSHV, converge in the ontogeny of germinal center (GC) or post-GC lymphomas. EBV oral transmission facilitates interactions with local bacteria and HPV, thereby increasing the risk of periodontal diseases and head and neck carcinomas. It is less clear as to how EBV is localized in the stomach, but together with Helicobacter pylori, they are known to be responsible for gastric cancer. Perhaps this mechanism is reminiscent of the local inflammation that attracts different herpesviruses and enhances graft damage and chances of rejection in transplanted patients. In this review, we discussed the existing evidence suggestive of EBV possessing the potential to synergize or cooperate with these agents to trigger or worsen the disease.
Asunto(s)
Coinfección/patología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/patogenicidad , Interacciones Microbiota-Huesped , Animales , Linfocitos B/inmunología , Linfocitos B/virología , Coinfección/microbiología , Coinfección/parasitología , Coinfección/virología , Infecciones por Virus de Epstein-Barr/inmunología , Centro Germinal/virología , Helicobacter pylori , Herpesvirus Humano 4/inmunología , Humanos , Ratones , Neoplasias Gástricas/virologíaRESUMEN
An association between varicella zoster virus (VZV) and multiple sclerosis (MS) has been reported in Mexican populations. The aim of this study was to compare the response of T cells from MS patients, during relapse and remission, to in vitro stimulation with VZV, adenovirus (AV) and Epstein-Barr virus (EBV). Proliferation and cytokine secretion of T cells from 29 relapsing-remitting MS patients and 38 healthy controls (HC) were analyzed by flow cytometry after stimulating with VZV, AV or EBV. IgG and IgM levels against VZV and EBV were quantified using Enzyme-Linked Immunosorbent Assay. Relapsing MS patients showed a higher percentage of responding CD4+ and CD8+ T cells against VZV compared to AV. In HC and remitting MS patients, proliferation of CD4+ T cells was higher when stimulated with VZV as compared to EBV. Moreover, T cells isolated from remitting patients secreted predominantly Th1 cytokines when cell cultures were stimulated with VZV. Finally, high concentration of anti-VZV IgG was found in sera from patients and controls. The results support previous studies of an VZV-MS association in the particular population studied and provide additional information about the possible role of this virus in the pathogenesis of MS.
Asunto(s)
Herpesvirus Humano 3/fisiología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/virología , Linfocitos T/inmunología , Adenoviridae/fisiología , Adulto , Anticuerpos Antivirales/inmunología , Citocinas/metabolismo , Femenino , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/fisiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/virología , Recurrencia , Inducción de RemisiónRESUMEN
Com grande distribuição mundial e incidência significativa, a toxoplamose é uma doença comum em mamíferos e pássaros, causada pelo protozoário Toxoplasma gondii. No homem, o parasitismo na fase proliferativa intracelular pode se apresentar sem sintomas, ou causar clínica transitória caracterizada por febre, fadiga e linfadenopatia. Por se tratar de patologia com sintomas inespecíficos e comuns a muitas outras, é fundamental a correta pesquisa de diagnósticos diferenciais, como citomegalovírus e Epstein-Barr. Relatamos o caso de um jovem e hígido, que desenvolveu pneumonia e, após confirmação sorológica para toxoplasmose e o tratamento adequado, apresentou melhora clínica.
With great worldwide distribution and significant incidence, toxoplamosis is a common disease in mammals and birds, caused by the protozoan Toxoplasma gondii. In humans, the parasitism in its intracellular proliferative phase may present no symptoms, or cause a transient condition characterized by fever, fatigue, and lymphadenopathy. Because it is a pathology with nonspecific symptoms that are common to many other conditions, it is fundamental to find the correct research of differential diagnoses, such as for Cytomegalovirus and Epstein Barr. We report a case of a young and healthy man who developed pneumonia and, after serological confirmation for toxoplasmosis and the appropriate treatment, presented clinical improvement
Asunto(s)
Humanos , Masculino , Adulto , Neumonía/etiología , Toxoplasmosis/complicaciones , Inmunocompetencia , Neumonía/tratamiento farmacológico , Neumonía/diagnóstico por imagen , Aspartato Aminotransferasas/análisis , Astenia , Proteína C-Reactiva/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Radiografía , Tomografía Computarizada por Rayos X , Toxoplasmosis/diagnóstico , Toxoplasmosis/inmunología , Infecciones por Citomegalovirus/diagnóstico , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/diagnóstico , Tos/diagnóstico , Citomegalovirus/inmunología , Diagnóstico Diferencial , Alanina Transaminasa/análisis , Fiebre/diagnóstico , Anemia , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: In developing countries, Epstein-Barr virus (EBV) infection is mostly asymptomatic in early childhood. EBV persistence may lead to different malignancies, such as B cell derived lymphomas. In Argentina, most children are seropositive at three years and an increased association between EBV and lymphoma was proved in children under 10 years old by our group. OBJECTIVE: Our aim was to characterize EBV infection at the site of entry and reactivation of viral infection -the tonsils- in order to better understand the mechanism of viral persistence in pediatric patients. METHODS: A cohort of 54 patients was described. We assessed specific antibodies profiles in sera; viral proteins presence by IHC on FFPE samples and EBV type from fresh tissue. RESULTS: EBV type 1 was prevalent, mostly in the youngest patients. Asymptomatic primary infected patients presented higher viral loads and Latency 0/I or II patterns, whereas the Latency III pattern was observed mostly in healthy carriers. There were no differences between groups in the expression of viral lytic antigens. This study discloses new features in patients undergoing primary infection from a developing population. Low viral inoculum and restricted viral antigen expression may be responsible for the lack of symptoms in children from our country.
Asunto(s)
Infecciones por Virus de Epstein-Barr/virología , Adolescente , Anticuerpos Antivirales/sangre , Antígenos Virales/metabolismo , Argentina , Niño , Preescolar , Países en Desarrollo , Femenino , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/metabolismo , Humanos , Lactante , Masculino , Tonsila Palatina/virología , Carga Viral , Proteínas Virales/metabolismo , Latencia del VirusRESUMEN
INTRODUCTION: This study assessed the seroprevalence of cytomegalovirus, associated factors, and Epstein-Barr virus coinfection among adult residents of Manaus. METHODS: Using a cross-sectional study design, we collected blood samples from 136 individuals in a household survey in 2016. Prevalence ratios were calculated using Poisson regression. RESULTS: Cytomegalovirus and Epstein-Barr virus seroprevalences were 67.6% (95% CI: 9.7-75.6%) and 97.8% (95% CI: 95.3-100.0%), respectively. Coinfection was observed in 66.2% (95% CI: 58.1-74.2%) of participants. Bivariate analysis showed no statistical association. CONCLUSIONS: Seroprevalences were high among participants and approximately 7 out of 10 individuals had cytomegalovirus and Epstein-Barr virus coinfection.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/inmunología , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4/inmunología , Adolescente , Adulto , Brasil/epidemiología , Coinfección , Estudios Transversales , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Virus de Epstein-Barr/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Factores Socioeconómicos , Adulto JovenRESUMEN
PURPOSE: To report a case of necrotizing scleritis associated with Epstein-Barr virus (EBV) infection. CASE REPORT: A 68-year-old woman with a history of scleral ulcer, perforation, and scleral graft, with initial negative studies for infectious processes and autoimmune systemic-diseases consulted our service for a second opinion after 2 years of treatment without improvement. She presented severe conjunctival and scleral hyperemia, vascular tortuosity in 360°, areas of scleral thinning and an elevated lesion of nodular appearance. EBV serologic antibody IgG titers were strongly positive and IgM titers were borderline. A scleral biopsy showed granulation tissue with severe inflammation without the presence of tumor cells; PCR was positive for EBV. The patient was treated with antiviral therapy with resolution of the scleritis. CONCLUSIONS: EBV although rare, should be considered as a differential diagnosis in patients with necrotizing scleritis with no improvement to conventional therapy.
Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones Virales del Ojo/diagnóstico , Esclerótica/patología , Escleritis/diagnóstico , Anciano , Anticuerpos Antivirales/análisis , Biopsia , ADN Viral/análisis , Diagnóstico Diferencial , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Humanos , Esclerótica/virología , Escleritis/virologíaRESUMEN
Abstract INTRODUCTION: This study assessed the seroprevalence of cytomegalovirus, associated factors, and Epstein-Barr virus coinfection among adult residents of Manaus. METHODS: Using a cross-sectional study design, we collected blood samples from 136 individuals in a household survey in 2016. Prevalence ratios were calculated using Poisson regression. RESULTS: Cytomegalovirus and Epstein-Barr virus seroprevalences were 67.6% (95% CI: 9.7-75.6%) and 97.8% (95% CI: 95.3-100.0%), respectively. Coinfection was observed in 66.2% (95% CI: 58.1-74.2%) of participants. Bivariate analysis showed no statistical association. CONCLUSIONS: Seroprevalences were high among participants and approximately 7 out of 10 individuals had cytomegalovirus and Epstein-Barr virus coinfection.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Infecciones por Citomegalovirus/epidemiología , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/epidemiología , Citomegalovirus/inmunología , Anticuerpos Antivirales/sangre , Factores Socioeconómicos , Brasil/epidemiología , Estudios Seroepidemiológicos , Prevalencia , Estudios Transversales , Factores de Riesgo , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Virus de Epstein-Barr/diagnóstico , Coinfección , Persona de Mediana EdadRESUMEN
This study aimed to verify the prevalence of IgG antibodies for Toxoplasma gondii, CMV, and EBV in tissue donors from different regions of Brazil between February 2016 and July 2017. In this retrospective study, 578 donors were evaluated from different regions of Brazil. The seroprevalence of T. gondii was 61.2%, CMV was 93%, and EBV was 98.3%. The seroprevalence increased with age, from 27.8% in donors younger than 18 years of age to 67.6% in those older than 60 years of age (p<0.05). The analysis of the seroprevalence of CMV and EBV showed similar percentages (>90%) among the different states, the interior and capital of Paraná state, sex, and age. The seroprevalence of CMV, EBV and TOXO is high in all groups and age in Brazilian donors of tissues.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/epidemiología , Infecciones por Virus de Epstein-Barr/epidemiología , Donantes de Tejidos , Toxoplasmosis/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Brasil , Citomegalovirus/inmunología , Femenino , Herpesvirus Humano 4/inmunología , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Seroepidemiológicos , Topografía Médica , Toxoplasma/inmunología , Adulto JovenRESUMEN
Aging immune deterioration and Epstein-Barr (EBV) intrinsic mechanisms play an essential role in EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV + DLBCLe) pathogenesis, through the expression of viral proteins, interaction with host molecules and epigenetic regulation, such as miR-155, required for induction of M1 phenotype of macrophages. This study aims to evaluate the relationship between macrophage polarization pattern in the tumor microenvironment and relative expression of miR-155 in EBV + DLBCLe and EBV-negative DLBCL patients. We studied 28 EBV + DLBCLe and 65 EBV-negative DLBCL patients. Tumor-associated macrophages (TAM) were evaluated by expression of CD68, CD163 and CD163/CD68 ratio (degree of M2 polarization), using tissue microarray. RNA was extracted from paraffin-embedded tumor samples for miR-155 relative expression study. We found a significantly higher CD163/CD68 ratio in EBV + DLBCLe compared to EBV-negative DLBCL. In EBV-negative DLBCL, CD163/CD68 ratio was higher among advanced-staged/high-tumor burden disease and overexpression of miR-155 was associated with decreased polarization to the M2 phenotype of macrophages. The opposite was observed in EBV + DLBCLe patients: we found a positive association between miR-155 relative expression and CD163/CD68 ratio, which was not significant after outlier exclusion. We believe that the higher CD163/CD68 ratio in this group is probably due to the presence of the EBV since it directly affects macrophage polarization towards M2 phenotype through cytokine secretion in the tumor microenvironment. Therapeutic strategies modulating miR-155 expression or preventing immuno-regulatory and pro-tumor macrophage polarization could be adjuvants in EBV + DLBCLe therapy since this entity has a rich infiltration of M2 macrophages in its tumor microenvironment.
Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Macrófagos/inmunología , MicroARNs/inmunología , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/inmunología , Antígenos de Diferenciación Mielomonocítica/metabolismo , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/fisiología , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/genética , Activación de Macrófagos/inmunología , Macrófagos/clasificación , Macrófagos/metabolismo , Masculino , MicroARNs/genética , Persona de Mediana Edad , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Epstein-Barr virus (EBV) is an oncogenic virus associated with the development of aggressive and poor-prognosis B-cell lymphomas in patients infected with human immunodeficiency virus (HIV+ patients). The most important risk factors for these malignancies include immune dysfunction, chronic immune activation, and loss of T-cell receptor (TCR) repertoire. The combination of all these factors can favor the reactivation of EBV, malignant cell transformation, and clinical progression toward B-cell lymphomas. The overarching aim of this study was to evaluate the frequency, phenotype, functionality, and distribution of TCR clonotypes for EBV-specific T-cell subpopulations in HIV+ patients at different clinical stages and for HIV+ patients with B-cell lymphoma, as well as to establish their association with clinical variables of prognostic value. Factors were studied in 56 HIV+ patients at different clinical stages and in six HIV+ subjects with diagnosed B-cell lymphoma. We found a significant decrease in all subpopulations of EBV-specific CD4+ T cells from HIV+ patients at stage 3 and with B-cell lymphoma. EBV-specific effector CD8+ T cells, particularly effector memory cells, were also reduced in HIV+ patients with B-cell lymphoma. Interestingly, these cells were unable to produce IFN-γ and lacked multifunctionality in HIV+ patients. The TCR-Vß repertoire, which is key for protection against EBV in healthy individuals, was less diverse in HIV+ patients due to a lower frequency of TCR-Vß2+, Vß4+, Vß7.1+, Vß9+, Vß13.6+, Vß14+, Vß17+, Vß22+ CD4+, Vß14+, and Vß17+ CD8+ T cells. HIV+ patients with positive plasma EBV loads (EBV+HIV+) had a noteworthy decrease in the levels of both TNF-α+ and multifunctional TNF-α+/IL-2+ and TNF-α+/IFN-γ+ CD8+ T cells. Altogether, our findings demonstrate that HIV+ patients have significant alterations in the immune response to EBV (poor-quality immunity) that can favor viral reactivation, escalating the risk for developing EBV-associated B-cell lymphomas.
Asunto(s)
Coinfección , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por VIH/inmunología , Herpesvirus Humano 4/inmunología , Interacciones Huésped-Patógeno/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Citocinas/metabolismo , Progresión de la Enfermedad , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/virología , Femenino , Infecciones por VIH/virología , Humanos , Inmunomodulación , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
Epstein Barr virus (EBV) gains access to the host through tonsillar crypts. Our aim was to characterize microenvironment composition around EBV+ cells in tonsils from pediatric carriers, to disclose its role on viral pathogenesis. LMP1 expression, assessed by immunohistochemistry (IHC), was used to discriminate EBV + and - zones in 41 tonsil biopsies. Three regions were defined: Subepithelial (SE), interfollicular (IF) and germinal center (GC). CD8, GrB, CD68, IL10, Foxp3, PD1, CD56 and CD4 markers were evaluated by IHC; positive cells/100 total cells were counted. CD8+, GrB+, CD68+ and IL10+ cells were prevalent in EBV+ zones at the SE region (p < 0.0001, p = 0.03, p = 0.002 and p = 0.002 respectively, Wilcoxon test). CD4+ and CD68+ cell count were higher in EBV + GC (p = 0.01 and p = 0.0002 respectively, Wilcoxon test). Increment of CD8, GrB and CD68 at the SE region could indicate a specific response that may be due to local homing at viral entry, which could be counterbalanced by IL10, an immunosuppressive cytokine. Additionally, it could be hypothesized that CD4 augment at the GC may be involved in the EBV-induced B-cell growth control at this region, in which macrophages could also participate.
Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Inmunidad Celular , Tonsila Palatina/patología , Tonsila Palatina/virología , Adolescente , Biomarcadores/análisis , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Proteínas de la Matriz Viral/análisisRESUMEN
Mycobacterium scrofulaceum is a slow-growing atypical mycobacteria with a reservoir in the environmen, and occasionally it causes disease in humans. The case of a 10-year-old patient with fever of four months of evolution is presented. Symptoms include bilateral adenopathies of neck, thorax, abdomen and inguinal region, rash, abdominal pain and vomiting; in addition, a positive serology for EBV and a culture of the left inguinal ganglia with growth of M. scrofulaceum were evidenced. Thus, this is the first report of human infection caused by the aforementioned mycobacterium in Ecuador, which it was particularly manifested with an unusual pattern of resistance.
Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/inmunología , Linfadenopatía/etiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium scrofulaceum/inmunología , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Humanos , Linfadenopatía/diagnóstico , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicacionesRESUMEN
Resumen Mycobacterium scrofulaceum es una micobacteria atípica de crecimiento lento que tiene como reservorio el ambiente. De forma ocasional causa enfermedad en humanos. Se presenta el caso de un niño de 10 años de edad con fiebre de cuatro meses de evolución, adenopatías cervicales, torácicas, abdominales e inguinales bilaterales, exantema, dolor abdominal y vómitos; con evidencia concomitante de serología positiva para el VEB y cultivo de los ganglios inguinales izquierdos con crecimiento de M. scrofulaceum. Es la primera comunicación de una infección causada por esta micobacteria en Ecuador, y que particularmente se presentó con un patrón de resistencia inusual.
Mycobacterium scrofulaceum is a slow-growing atypical mycobacteria with a reservoir in the environmen, and occasionally it causes disease in humans. The case of a 10-year-old patient with fever of four months of evolution is presented. Symptoms include bilateral adenopathies of neck, thorax, abdomen and inguinal region, rash, abdominal pain and vomiting; in addition, a positive serology for EBV and a culture of the left inguinal ganglia with growth of M. scrofulaceum were evidenced. Thus, this is the first report of human infection caused by the aforementioned mycobacterium in Ecuador, which it was particularly manifested with an unusual pattern of resistance.
Asunto(s)
Humanos , Masculino , Niño , Mycobacterium scrofulaceum/inmunología , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/diagnóstico , Linfadenopatía/etiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Linfadenopatía/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/complicacionesRESUMEN
El linfoma difuso de células B grandes (LDCBG) es el linfoma más frecuente. La presentación clínica puede ser nodal o extranodal y sus síntomas dependen de la localización tumoral; en la mayoría de los casos están asociados a algún tipo de inmunodeficiencia. Referiremos un caso de LDCBG de presentación atípica en una localización muy infrecuente. Es importante tener en cuenta estas situaciones, ya que pueden simular otros procesos patológicos, retrasando así su correcto diagnóstico y por lo tanto un adecuado tratamiento. (AU)
Diffuse large cell lymphoma B (LDCBG) is the most common type of lymphoma. It´s clinical presentation can be nodal or extranodal and it's symptoms depend where the tumor is located and whether is associated or not with an immunodeficiency disease. We present an atypical presentation of a LDCBG in a very unusual location. It´s important to consider these kind of appearance, as they can mimic other oral pathological processes, delaying their correct diagnosis and therefore an appropriate treatment. (AU)
Asunto(s)
Humanos , Masculino , Anciano , Linfoma no Hodgkin/diagnóstico , Neoplasias Gingivales/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma no Hodgkin/clasificación , Linfoma no Hodgkin/etiología , Neoplasias de la Boca/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Seronegatividad para VIH/inmunología , Herpesvirus Humano 4/inmunología , Úlceras Bucales/patología , Mucosa Bucal/patologíaRESUMEN
INTRODUCTION: Hematopoietic stem cell transplantation in pediatric patients is an alternative treatment for different diseases. The conditioning regimen for transplant predisposes recipients to the development of infections. Viral infections by herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human cytomegalovirus (CMV), and Epstein-Barr virus (EBV), are the most common, and the leading cause of morbidity and mortality among these patients. These viruses lie dormant in various cell types and the reactivation of latent infections may lead to asymptomatic viral shedding in saliva. The detection of these viruses in secretions may contribute to understand the behavioral dynamics of these viral infections in transplanted patients, and to the early diagnosis of reactivation. OBJECTIVE: To assess HSV-1, HSV-2, CMV and EBV viral shedding in the saliva of patients admitted for hematopoietic stem cell transplantation at Fundación HOMI - Hospital de la Misericordia between January and November of 2012. MATERIALS AND METHODS: We evaluated stimulated saliva samples of 17 hematopoietic stem cell transplantation recipients weekly. We performed DNA extraction from saliva, and we evaluated the presence of DNA for HSV-1, HSV-2, CMV, and EBV by PCR. RESULTS: While we detected HSV-2 and CMV DNA in the saliva of four patients, EBV DNA was detected in nine patients with leukopenia. In contrast, we did not detect HSV-1 DNA in saliva. Additionally, four out of the 17 patients showed a simultaneous shedding of CMV and EBV. CONCLUSIONS: By conventional PCR, we demonstrated asymptomatic HSV-2, CMV, and EBV viral shedding in saliva, associated with leukopenia.