RESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. METHODS: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). RESULTS: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). CONCLUSIONS: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.
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Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Inmunoglobulina A , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Detección Precoz del Cáncer/métodos , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/sangre , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Sensibilidad y Especificidad , Pruebas Serológicas/métodosRESUMEN
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/terapia , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Rituximab/uso terapéutico , Trasplante Homólogo/efectos adversosRESUMEN
INTRODUCTION: This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. METHODS: This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. RESULTS: Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. CONCLUSION: This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Trasplante de Riñón , Trastornos Linfoproliferativos , Complicaciones Posoperatorias , Carga Viral , Humanos , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/virología , Trastornos Linfoproliferativos/etiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Persona de Mediana Edad , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Factores de Edad , Complicaciones Posoperatorias/virología , Complicaciones Posoperatorias/diagnóstico , Viremia/diagnóstico , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéuticoRESUMEN
A 62-year-old man presented with fever and anorexia since July X. Initial treatments were rendered ineffective, and due to altered consciousness and vomiting, he was referred to our hospital. On admission, he manifested delirium, drowsiness, and disorientation. While blood tests were normal, gastroscopy identified a type 3 tumor in his lower gastric body, later diagnosed as a poorly differentiated adenocarcinoma. Immunohistochemistry demonstrated negative human epidermal growth factor receptor 2 and positive programmed death-ligand 1 expression with a combined positive score ≥5. Furthermore, a positive Epstein-Barr virus-encoded small RNA in situ hybridization result was noted. Abdominal contrast-enhanced CT and PET-CT scans demonstrated multiple lymph node metastases around the stomach and liver, establishing the diagnosis of stage IVB gastric cancer (T4aN2M1). Brain magnetic resonance imaging (MRI) demonstrated enhanced lesions in the brainstem, cerebellar sulci, and right occipital lobe. Although cerebrospinal fluid cytology was negative for malignancy, the clinical symptoms and MRI findings confirmed leptomeningeal carcinomatosis (LMC). The patient underwent radiotherapy for LMC (total of 30Gy in 10 fractions), followed by combination therapy with a nivolumab and SOX regimen. Posttreatment, the LMC symptoms resolved;however, he experienced grade 3 immune-related adverse events related to liver dysfunction. Nivolumab was discontinued, and with steroid administration, the adverse events improved. Imaging evaluations posttreatment showed gastric tumor reduction and the absence of LMC. After 7 cycles, nivolumab was reintroduced, with no liver dysfunction recurrence noted through 15 cycles. Endoscopic examination 1 year postonset demonstrated that the gastric tumor had scarred, and MRI showed no signs of LMC recurrence. In 5-8% of solid tumors, LMC complications are present, resulting in limited treatment options and poor prognosis. Recent reports suggest the potential of immune checkpoint inhibitors in treating intracranial metastasis from solid tumors. In Japan, nivolumab was approved for gastric cancer treatment in 2017 and for first-line therapy in combination with chemotherapy since 2021. We report a case in which radiotherapy and chemotherapy combined with nivolumab provided durable control of LMC originating from gastric cancer for more than 1 year.
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Infecciones por Virus de Epstein-Barr , Carcinomatosis Meníngea , Nivolumab , Neoplasias Gástricas , Humanos , Masculino , Persona de Mediana Edad , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Carcinomatosis Meníngea/secundario , Infecciones por Virus de Epstein-Barr/complicaciones , Resultado del Tratamiento , Herpesvirus Humano 4/aislamiento & purificaciónRESUMEN
AIMS: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. METHODS: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. FINDINGS: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. CONCLUSION: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.
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Virus BK , Infecciones por Citomegalovirus , Citomegalovirus , Infecciones por Virus de Epstein-Barr , Rechazo de Injerto , Herpesvirus Humano 4 , Trasplante de Riñón , Infecciones por Polyomavirus , Carga Viral , Viremia , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Virus BK/aislamiento & purificación , Virus BK/genética , Adulto , Estudios Transversales , Infecciones por Polyomavirus/virología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , Rechazo de Injerto/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Irán/epidemiología , Factores de Riesgo , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/sangre , Anciano , Adulto Joven , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
Steroid usage poses a risk of Clostridioides difficile infection (CDI), but high-dose corticosteroid treatment can lead to false-negative CD toxin test results. Moreover, CDI-induced nausea can complicate administration of oral antibiotics, which are typically the primary therapy for CDI. In the present case, a 43-year-old woman diagnosed with EBV-associated T-cell post-transplant lymphoproliferative disorder developed CDI during treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Following five cycles of CHOP, the patient presented with nausea and diarrhea. CT scans revealed swelling in the ileocecal to transverse area of the colon. While the glutamate dehydrogenase (GDH) antigen test result was positive, the CD toxin test result was negative. However, the nucleic amplification test (NAAT) result was positive, confirming the diagnosis of CDI. Oral treatment with fidaxomicin was initially impractical due to persistent nausea. Instead, treatment began with intravenous metronidazole, and was later switched to fidaxomicin pills. Symptoms improved notably within 10 days, and the patient ultimately made a complete recovery. This case underscores the significance of exploring alternative approaches to CDI management, particularly in immunosuppressed patients.
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Infecciones por Clostridium , Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Técnicas de Amplificación de Ácido Nucleico , Humanos , Femenino , Adulto , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Clostridioides difficile , Herpesvirus Humano 4 , Linfocitos TRESUMEN
BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer is one of the mature B-cell lymphoproliferative diseases occurring in patients with immune dysfunction including those with immunosuppressive treatment such as methotrexate. CASE PRESENTATION: A Japanese elderly man in his 80s with rheumatoid arthritis on methotrexate was admitted to our hospital complaining persistent pharyngeal pain. Laboratory tests revealed severe pancytopenia, elevated C-reactive protein, and increased creatinine levels. An otolaryngological examination showed ulceration of the right tonsil, from which diagnostic biopsy was performed. The diagnosis of Epstein-Barr virus-positive mucocutaneous ulcer was made and bone marrow aspiration revealed hypocellularity and megaloblastic changes. Pancytopenia was improved after discontinuing methotrexate, and repeated bone marrow aspiration test revealed recovery of normal cellularity and disappearance of dysplasia, confirming the diagnosis of methotrexate intoxication. Tonsil ulcer was improved only with discontinuation of methotrexate, which strongly supported the diagnosis of EBV-MCU. CONCLUSION: Our case suggested that even this best prognosis form of lymphoproliferative disease could lead to fatal complications if not appropriately managed.
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Artritis Reumatoide , Infecciones por Virus de Epstein-Barr , Metotrexato , Humanos , Metotrexato/efectos adversos , Masculino , Infecciones por Virus de Epstein-Barr/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Anciano de 80 o más Años , Úlcera/inducido químicamente , Inmunosupresores , Trastornos Linfoproliferativos/inducido químicamente , Herpesvirus Humano 4/aislamiento & purificación , Pancitopenia/inducido químicamente , Tonsila Palatina/patologíaRESUMEN
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that has been related to oncogenesis of lymphoid and epithelial malignancies. Although the mechanism of EBV infection of NK and T cells remains enigmatic, it plays a pathogenic role in various EBV+ NK-cell and T-cell lymphoproliferative diseases (LPDs), through promotion of cell activation pathways, inhibition of cell apoptotic pathways, behaving as oncogenes, interacting with host oncogenes or acting epigenetically. The study of NK-cell LPDs, previously hampered by the lack of immunophenotypical and genotypical criteria of NK cells, has become feasible with the recently accepted criteria. EBV+ NK- and T-cell LPDs are mostly of poor prognosis. This review delivers a short history from primeval to recent EBV+ NK- and T-cell LPDs in non-immunocompromised subjects, coupled with increasing interest, and work on the biological and oncogenic roles of EBV.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Células Asesinas Naturales , Trastornos Linfoproliferativos , Linfocitos T , Humanos , Trastornos Linfoproliferativos/virología , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Células Asesinas Naturales/virología , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
The relationship between Toll-like receptors (TLRs) and prostate cancer (PCa) is complex due to the presence of the Epstein-Barr virus (EBV) infection, which has been identified as a predisposing factor for some cancers, including PCa. The present study aims to investigate these complex links by examining the levels of selected TLRs and the potential impact of EBV infection on PCa. Therefore, we examined the serum of patients with PCa. The study compared EBV(+) patients to risk groups, the Gleason score (GS), and the T-trait. Additionally, the correlation between TLR and antibody levels was examined. The results indicated that higher levels of TLR-2 and TLR-9 were observed in more advanced PCa. The findings of this study may contribute to a deeper understanding of the role of viral infections in PCa and provide information on future strategies for the diagnosis, prevention, and treatment of these malignancies.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neoplasias de la Próstata , Receptor Toll-Like 2 , Receptor Toll-Like 9 , Humanos , Masculino , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/virología , Receptor Toll-Like 2/sangre , Receptor Toll-Like 2/metabolismo , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Anciano , Persona de Mediana Edad , Clasificación del TumorRESUMEN
OBJECTIVE: To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI). METHODS: EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed. RESULTS: In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and ß2-microglobulinï¼ß2-MGï¼, poorer coagulation, and lower soluble IL-2 receptor ï¼sCD25ï¼. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes ï¼KDIGOï¼classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, ß2-MG, activated partial thromboplastin time ï¼APTTï¼, and prothrombin time activity ï¼PTAï¼were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit ï¼ICUï¼, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, ß2-MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days. CONCLUSION: AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.
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Lesión Renal Aguda , Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Humanos , Lesión Renal Aguda/etiología , Estudios Retrospectivos , Pronóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Mortalidad Hospitalaria , Femenino , MasculinoRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. METHODS: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. RESULTS: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56+ cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. CONCLUSIONS: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Estudios Retrospectivos , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/sangre , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Anciano , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Factores de Riesgo , Pronóstico , Adulto , Curva ROC , China/epidemiología , Anticuerpos Antivirales/sangre , ADN Viral/sangreRESUMEN
Epstein-Barr virus (EBV) is a ubiquitous and predominantly B cell tropic virus. One of the most common viruses to infect humans, EBV, is best known as the causative agent of infectious mononucleosis (IM). Although most people experience asymptomatic infection, EBV is a potent immune stimulus and as such it elicits robust proliferation and activation of the B-lymphocytes it infects as well as the immune cells that respond to infection. In certain individuals, such as those with inherited or acquired defects affecting the immune system, failure to properly control EBV leads to the accumulation of EBV-infected B cells and EBV-reactive immune cells, which together contribute to the development of often life-threatening cytokine storm syndromes (CSS). Here, we review the normal immune response to EBV and discuss several CSS associated with EBV, such as chronic active EBV infection, hemophagocytic lymphohistiocytosis, and post-transplant lymphoproliferative disorder. Given the critical role for cytokines in driving inflammation and contributing to disease pathogenesis, we also discuss how targeting specific cytokines provides a rational and potentially less toxic treatment for EBV-driven CSS.
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Síndrome de Liberación de Citoquinas , Citocinas , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Herpesvirus Humano 4/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Citocinas/inmunología , Citocinas/metabolismo , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/virología , Linfocitos B/inmunología , Linfocitos B/virología , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/virología , AnimalesAsunto(s)
Coinfección , Infecciones por Virus de Epstein-Barr , Infecciones por Herpesviridae , Herpesvirus Humano 4 , Herpesvirus Humano 8 , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Coinfección/virología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Masculino , Persona de Mediana Edad , FemeninoAsunto(s)
Herpesvirus Humano 4 , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/genética , Carcinoma/virología , Carcinoma/genéticaRESUMEN
The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4+ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4+ T-cell count, the patient had normal counts of CD3+ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2+ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA-CD27+CCR7+ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4+ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.
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Epidermodisplasia Verruciforme , Proteínas Serina-Treonina Quinasas , Humanos , Epidermodisplasia Verruciforme/genética , Epidermodisplasia Verruciforme/diagnóstico , Masculino , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/deficiencia , Adulto , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/etiología , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/diagnóstico , Mutación/genética , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Linfocitos Intraepiteliales/inmunología , ConsanguinidadRESUMEN
PURPOSE: To find an association between oral mucosal human papilloma- and/or Epstein-Barr (HPV, EBV) virus infection in patients with dry mouth and/or Sjögren's syndrome (SS) compared to healthy controls and to find connections with salivary gland histopathological alterations. MATERIALS AND METHODS: Ninety-two participants were divided into four groups: 1. healthy controls (n = 32); 2. xerostomia (n = 28); 3. hyposalivation (n = 22); and 4. SS groups (n = 10). To detect virus infection brush biopsy was outlined in all groups. Detections of virus-specific sequences were achieved with polymerase chain reaction (PCR). Lip biopsy and histopathological assessment was performed in groups 2, 3 and 4. RESULTS: HPV positivity of oral mucosal cells was shown in group 1: 1 (3.12%); group 2: 3 (10.7%); group 3: 2 (8.26%); and in group 4: 0 of the samples. EBV was present in group 1: 14 (43.7%); group 2: 17 (60.7%); group 3: 6 (27.3%); and in group 4: 5 (50%) of the cases. There was no statistically significant difference between the attributes. Intact salivary gland in 28.2%, chronic sialadenitis in 28.2%, stromal fibrosis in 6.5%, lipomatous atrophy in 8.6%, fibrous atrophy in 6.5% and positive focus score (SS) in 26.1% were found in the subjects. Neither HPV nor EBV infection caused statistically significantly more histological abnormalities. CONCLUSION: Orofacial mucosal HPV and/or EBV DNA rates did not differ statistically significantly in patients with xerostomia or hyposalivation or SS compared to healthy controls, therefore, it cannot prove the provocative role of these viruses in dry mouth and/or SS. Neither dry mouth nor SS were accompanied by statistically significantly more salivary gland alterations in HPV- and/or EBV-positive subjects; these alterations are frequent in the virus-negative cases too.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Mucosa Bucal , Síndrome de Sjögren , Xerostomía , Humanos , Síndrome de Sjögren/virología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Femenino , Mucosa Bucal/virología , Mucosa Bucal/patología , Persona de Mediana Edad , Masculino , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Hungría , Infecciones por Papillomavirus/virología , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Glándulas Salivales/patología , Glándulas Salivales/virología , ADN Viral/análisis , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Virus del Papiloma HumanoRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients. METHODS: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival. RESULTS: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up. CONCLUSION: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Trasplante de Riñón , Complicaciones Posoperatorias , Tumor de Músculo Liso , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Tumor de Músculo Liso/virología , Tumor de Músculo Liso/etiología , Tumor de Músculo Liso/patología , Tumor de Músculo Liso/diagnóstico , Adulto , Estudios de Seguimiento , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/aislamiento & purificación , Pronóstico , Francia/epidemiología , Adolescente , Adulto Joven , Niño , Complicaciones Posoperatorias/diagnóstico , Rechazo de Injerto/etiología , Fallo Renal Crónico/cirugía , Supervivencia de Injerto , Factores de Riesgo , Pruebas de Función Renal , Tasa de Filtración Glomerular , Tasa de SupervivenciaRESUMEN
We present a case of atraumatic splenic rupture secondary to Epstein-Barr virus (EBV) infection in a woman in her early 50s. The patient initially presented with sepsis secondary to pneumonia but then developed abdominal pain and distension. CT revealed splenic rupture with a significant perisplenic hematoma. Laboratory tests confirmed an EBV infection. Owing to frailty, she underwent fluoroscopy-guided splenic artery embolisation. This case highlights the rare risk of splenic rupture following EBV infection, even in the absence of typical symptoms of infectious mononucleosis.
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Embolización Terapéutica , Infecciones por Virus de Epstein-Barr , Rotura del Bazo , Humanos , Femenino , Rotura del Bazo/etiología , Rotura del Bazo/diagnóstico por imagen , Rotura del Bazo/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Persona de Mediana Edad , Rotura Espontánea , Embolización Terapéutica/métodos , Tomografía Computarizada por Rayos X , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/virología , Arteria Esplénica/diagnóstico por imagen , Dolor Abdominal/etiologíaRESUMEN
Multiple Sclerosis (MS) is a complex neurological disease which prevalence is increasing worldwide. The impact of environmental factors on MS susceptibility has already been defined and highlighted in many previous reports, particularly vitamin D or ultraviolet B light exposure, Epstein-Barr virus (EBV) infection, obesity, and smoking. There is increasing evidence that environmental and lifestyle factors are not only important in triggering MS but are also implicated in MS progression. Low sun exposure and vitamin D deficiency exhibit a strong relationship with disease progression in both animal and human studies. The gestational period seems also to impact long-term disease progression as January's babies had a higher risk of requiring walking assistance than those born in other months. The implication of EBV in neurodegeneration and MS progression was also suggested even though its specific targets and mechanisms are still unclear. Cigarette smoking is correlated with faster clinical progression. The association of obesity and smoking seems to be associated with a faster progression and an increased rate of brain atrophy. Although the effect of air pollution on MS pathogenesis remains not fully understood, exposure to polluted air can stimulate several mechanisms that might contribute to MS severity. People with MS with active disease have an altered microbiota compared to patients in the remission phase. Cardiovascular comorbidities, epilepsy, and depression are also associated with a more severe disability accrual. Knowledge about MS modifiable risk factors of progression need to be incorporated into everyday clinical practice in order to ameliorate disease outcomes.
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Progresión de la Enfermedad , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/etiología , Factores de Riesgo , Exposición a Riesgos Ambientales/efectos adversos , Animales , Infecciones por Virus de Epstein-Barr/complicacionesRESUMEN
BACKGROUND: As a common chronic recurrent inflammatory skin disease, psoriasis is characterized by erythema and scaly skin lesions, with infection as an integral part of the pathogenesis of many diseases. Many previous cases reported the impact of psoriasis on infection. However, the existing research fails to completely clarify the infection factors associated with the potential of these diseases and causality. MATERIALS AND METHODS: Thirteen kinds of pathogens and their immune responses and psoriasis in the phenotype of 46 species of SNPs data were respectively obtained from the GWAS catalog database and the UK biobank database. With the help of R software, three methods of inverse variance weighted (IVW), weighted median (WME), and MR-Egger regression were used to analyze the causality of the dataset. RESULTS: According to the results of IVW analysis, there is a causal relationship between anti-Epstein Barr virus antibody and psoriasis (OR: 1.003, 95% CI: 1.001â¼1.006, P = 0.046) with a positive correlation. CONCLUSION: Based on the results of MR analysis, there is a causal relationship between psoriasis and EBV infection, which indicates that EBV infection can increase the risk or severity of psoriasis. Therefore, in clinical scenarios, patients afflicted with psoriasis should be prevented from contracting the infection and recurrence of EBV as well as symptoms of psoriasis. The underlying immunological mechanism also provides a new perspective for experimental research.