RESUMEN

Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein-Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC. Plasma EBV DNA load, IL-6 level, VEGF expressions were measured in 24 patients with NPC at presentation and various time points during and after treatment. There was a positive correlation between high plasma EBV DNA load with higher IL-6 and VEGF expression, which was closely associated with therapeutic response as well. Persistent or recurrent plasma EBV load with higher IL-6 and VEGF levels can potentially predict disease progression and may be useful to select patients for additional therapy and longer follow-up.

Asunto(s)

Carcinoma , ADN Viral , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Interleucina-6 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Factor A de Crecimiento Endotelial Vascular , Carga Viral , Humanos , Interleucina-6/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico , Herpesvirus Humano 4/genética , Femenino , Masculino , ADN Viral/sangre , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular/sangre , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico , Adulto , Pronóstico , Carcinoma/virología , Carcinoma/sangre , Carcinoma/diagnóstico , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/diagnóstico , Biomarcadores/sangre , Anciano , Plasma/virología

RESUMEN

Introduction: Intra-tumoral B cells mediate a plethora of immune effector mechanisms with key roles in anti-tumor immunity and serve as positive prognostic indicators in a variety of solid tumor types, including epithelial ovarian cancer (EOC). Several aspects of intra-tumoral B cells remain unclear, such as their state of activation, antigenic repertoires, and capacity to mature into plasma cells. Methods: B lymphocytes were isolated from primary EOC tissue and malignant ascites and were maintained in cell culture medium. The stably maintained cell lines were profiled with flow cytometry and B cell receptor sequencing. Secreted antibodies were tested with a human proteome array comprising more than 21,000 proteins, followed by ELISA for validation. Originating tumor samples were used for spatial profiling with chip cytometry. Results: Antibody-secreting B lymphocytes were isolated from the ovarian tumor microenvironment (TME) of four different EOC patients. The highly clonal cell populations underwent spontaneous immortalization in vitro, were stably maintained in an antibody-secreting state, and showed presence of Epstein-Barr viral (EBV) proteins. All originating tumors had high frequency of tumor-infiltrating B cells, present as lymphoid aggregates, or tertiary lymphoid structures. The antigens recognized by three of the four cell lines are coil-coil domain containing protein 155 (CCDC155), growth factor receptor-bound protein 2 (GRB2), and pyruvate dehydrogenase phosphatase2 (PDP2), respectively. Anti-CCDC155 circulating IgG antibodies were detected in 9 of 20 (45%) of EOC patients' sera. Tissue analyses with multiparameter chip cytometry shows that the antibodies secreted by these novel human B cell lines engage their cognate antigens on tumor cells. Discussion: These studies demonstrate that within the tumor-infiltrating lymphocyte population in EOC resides a low frequency population of antibody-secreting B cells that have been naturally exposed to EBV. Once stably maintained, these novel cell lines offer unique opportunities for future studies on intratumor B cell biology and new target antigen recognition, and for studies on EBV latency and/or viral reactivation in the TME of non-EBV related solid tumors such as the EOC.

Asunto(s)

Ascitis , Linfocitos B , Herpesvirus Humano 4 , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/inmunología , Herpesvirus Humano 4/inmunología , Linfocitos B/inmunología , Ascitis/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Latencia del Virus/inmunología , Microambiente Tumoral/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Carcinoma Epitelial de Ovario/inmunología , Anticuerpos Antivirales/inmunología , Línea Celular Tumoral

RESUMEN

Plasmablastic lymphoma (PBL) is a rare and aggressive type of lymphoma, particularly affecting HIV-positive and immunocompromised individuals, with a median diagnosis age of 49 years. Cases of this malignancy in HIV-negative individuals are less common and rarely involve the bone marrow. While traditional chemotherapy regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) were previously utilized in the management of such malignancy, the National Comprehensive Cancer Network currently recommends more intensive approaches. We present a rare stage IV Epstein-Barr virus (EBV)-positive PBL with a nasal cavity tumor extending into the left orbital sinus and encapsulating segments of the optic nerve in a 38-year-old young immunocompetent adult, without a significant past medical history. Treatment consisted of 6 cycles of Bortezomib in combination with dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and intrathecal methotrexate which exhibited significant clinical and radiological improvement suggesting the potential efficacy of this regimen. Vision returned to baseline, the mass size reduced significantly, and headaches improved. Given this outcome, it is highly encouraged to emphasize the need for further exploration of this treatment in larger clinical trials.

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/genética

RESUMEN

Pure red cell aplasia (PRCA) is a rare hematologic disorder presenting with symptomatic normocytic anemia with preservation of other bone marrow cell lineages that may be acquired in adulthood due to malignancy, autoimmune disease, and infections. PRCA has been attributed to Epstein-Barr virus (EBV) in patients with underlying malignancy; however, we present a rare case of EBV-related PRCA in a previously healthy elderly male without an underlying malignancy who developed transfusion-dependent anemia that responded to glucocorticoids, rituximab, and intravenous immunoglobulins.

RESUMEN

Background: Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Methods: Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. Results: TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. Conclusion: We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

RESUMEN

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.

Asunto(s)

Enfermedad Relacionada con Inmunoglobulina G4 , Inmunoglobulina G , Neoplasias Nasofaríngeas , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/diagnóstico , Masculino , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Diagnóstico Diferencial , Femenino , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/inmunología , Células Plasmáticas/inmunología

Asunto(s)

Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neoplasias , Linfocitos T , Humanos , Herpesvirus Humano 4/inmunología , Neoplasias/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Linfocitos T/inmunología , Animales

RESUMEN

BACKGROUND: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. METHODS: A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. RESULTS: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. CONCLUSIONS: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.

Asunto(s)

Anticuerpos Antivirales , Detección Precoz del Cáncer , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Inmunoglobulina A , Inmunoglobulina G , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , China/epidemiología , Femenino , Persona de Mediana Edad , Herpesvirus Humano 4/inmunología , Estudios Prospectivos , Anticuerpos Antivirales/sangre , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/epidemiología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/sangre , Adulto , Inmunoglobulina A/sangre , Detección Precoz del Cáncer/métodos , Inmunoglobulina G/sangre , Anciano , Estudios de Casos y Controles , Modelos de Riesgos Proporcionales , Pueblos del Este de Asia

RESUMEN

In this case report, we present a 53-year-old immunocompetent male exhibiting cholecystitis and cardiomyopathy related to cytomegalovirus (CMV) infection. The initial presentation pointed toward cholecystitis, including epigastric pain, chronic dysgeusia, dyspepsia, and cholelithiasis on ultrasound. A cholecystectomy was performed, and tissue analysis showed subacute cholecystitis. Postsurgical daily fever spikes prompted subsequent evaluation, which revealed CMV infection along with cardiomyopathy as evidenced by a reduced left ventricular ejection fraction, despite no suggestive clinical symptoms. Gastrointestinal symptoms, along with elevated liver enzymes, indicated possible congestive hepatopathy. Preceding symptoms also suggested a viral etiology, including a protracted fever and a possible transient Bell's palsy. Medical management for viral myocarditis was initiated, and the patient has been followed closely after discharge. The case emphasizes the importance of considering viral etiology with comprehensive cardiac workup, even in the absence of overt cardiac symptoms but with abnormal liver enzymes. Surprisingly, the infectious workup showed positive West Nile virus (WNV) and Epstein-Barr virus (EBV) serology, indicating possible co-infection or cross-reactivity.

RESUMEN

Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in two B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.

RESUMEN

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), is a common viral illness among adolescents and young adults. IM typically presents with symptoms such as fever, lymphadenopathy, and pharyngitis. We present a case of a 32-year-old woman who developed a maculopapular rash following ibuprofen administration, revealing an underlying undiagnosed IM. Laboratory investigations confirmed EBV infection. This represents the first documented case linking non-steroidal anti-inflammatory drugs (NSAIDs) to IM presentation. Awareness of this association is crucial for timely diagnosis and management, especially when evaluating patients with unexplained skin reactions to medications.

RESUMEN

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) secondary to acute lymphoblastic leukemia (ALL) is a rare disease with poor prognosis, usually attributed to delayed diagnosis. To date, only four cases of ALL developing DLBCL have been reported, while none of them exhibiting central nervous system (CNS) symptoms. CASE DESCRIPTION: Here, we report an unusual case of a 15-year-old boy diagnosed with ALL and treated based on the SCCLG-ALL 2016 protocol. While he was receiving maintenance treatment, the patient developed dizziness and vomiting. An Epstein-Barr virus (EBV)-positive DLBCL with CNS involvement was diagnosed from inguinal lymph nodes biopsy, EBV DNA tests and head magnetic resonance imaging (MRI). Meanwhile, a dramatic decrease of immune cells and immunoglobulin was detected in the occurrence of DLBCL. He received therapy based on SCCCG-NHL-2017 protocol immediately after the diagnosis. CONCLUSIONS: We present the first retrospective report of four cases of non-Hodgkin lymphoma (NHL) secondary to ALL between 1990 and 2022. The pathogenesis of secondary DLBCL may be related to infection, immunodeficiency, genetic susceptibility, and treatment. Thus, the detection of EBV DNA during the full course of ALL therapy and genetic tests were needed in the occurrence of secondary DLBCL. Given to the rare rate and insufficient treatment experience, longer follow-up and enough sample size are needed.

Asunto(s)

Linfoma de Células B Grandes Difuso , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Masculino , Adolescente , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico

RESUMEN

BACKGROUND: Kidney transplantation in Sudan is funded by the government. Cytomegalovirus prophylaxis is provided for patients who receive biological induction or have recipient-negative donor-positive cytomegalovirus serology. Doctor Selma Center for Kidney Diseases joined the national kidney transplant program in May 2019. Since then, we observed the frequent occurrence of cancer in patients who received modest immunosuppression without viral prophylaxis. METHODS: We retrospectively divided kidney transplant recipients between 2019 and 2021 into two groups according to cytomegalovirus prophylaxis and compared tumor occurrence rates. RESULTS: The first group included 77 patients who did not receive biological induction or cytomegalovirus prophylaxis. The second group included 92 patients who received valganciclovir for 3-6 months. There was no other antiviral treatment except entecavir for chronic hepatitis B virus infection in eight patients. Five patients in the first group developed malignancy. The first patient presented eight months post-transplant with Kaposi sarcoma of the stomach and responded to treatment with sirolimus. The second patient presented nine months post-transplant with cutaneous Kaposi sarcoma and also responded to sirolimus. Two patients presented two and four months post-transplant with aggressive non-cutaneous Kaposi sarcoma that involved the gastrointestinal tract and lymphatic system and died soon afterwards. The fifth patient presented three years post-transplant with non-Hodgkin lymphoma of the duodenum and is currently receiving chemotherapy. Malignancy rate (6.5% vs 0.0%, P = 0.02) and Kaposi sarcoma rate (5.2% vs 0.0%, P = 0.04) were significantly higher in the first group. CONCLUSION: In Sudan, omitting valganciclovir prophylaxis after kidney transplantation was associated with a high rate of virus-induced malignancy.

RESUMEN

Hydroa vacciniforme lymphoproliferative disorder (HVLPD) is a rare disease related to Epstein-Barr virus (EBV), mainly in children, and is an EBV-associated cutaneous T and natural killer (NK) cell lymphoproliferative disorder. The disorder in some patients may progress to EBV-associated systemic T or NK-cell lymphoma. To summarize the characteristics of HVLPD in Chinese paediatric patients and to examine the risk factors indicating poor prognosis. We performed a retrospective analysis of patients with HVLPD from the Department of Dermatology, Beijing Children's Hospital. Based on diagnosis, medical history, examination results, and immunophenotype, we analysed HVLPD in 42 paediatric cases in order to examine the clinical features, prognoses, and risk factors. Forty-two paediatric patients were enrolled, with a median onset age of five years. All patients presented with papulovesicular lesions, and 32 systemic HVLPD (sHVLPD) patients had systemic symptoms, including fever, lymphadenopathy, hepatomegaly, splenomegaly, and liver dysfunction. Of the sHVLPD cases, 13 also had severe mosquito bite allergy (SMBA). Twenty-five cases were T-type, and nine were CD56+-dominant type. Follow-up data showed that 12 patients had complete remission, and three patients died. SMBA is a risk factor for disease progression in patients with HVLPD, and the pathological CD56+-dominant phenotype is associated with poor prognosis.

Asunto(s)

Hidroa Vacciniforme , Humanos , Estudios Retrospectivos , Masculino , Hidroa Vacciniforme/virología , Hidroa Vacciniforme/patología , Femenino , Preescolar , Niño , Lactante , Adolescente , Pronóstico , Trastornos Linfoproliferativos/virología , Trastornos Linfoproliferativos/patología , Infecciones por Virus de Epstein-Barr/complicaciones , Factores de Riesgo , China/epidemiología , Herpesvirus Humano 4/aislamiento & purificación , Hepatomegalia/virología

RESUMEN

EBV-positive nodal T- and NK-cell lymphoma (EBV+ NT/NKCL) is a recently recognized entity in the 5th edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Notably, CD30 positivity is frequently observed in (EBV+ NT/NKCL), creating diagnostic challenges to distinguish it from ALK-negative anaplastic large cell lymphoma (ALCL). Furthermore, cases of EBV+ ALCL have been documented in the literature, predating the inclusion of EBV+ nodal cytotoxic T-cell lymphoma as a variant of peripheral T-cell lymphoma. We present a case of a 47-year-old male presenting with multiple lymphadenopathies. The histomorphologic and immunophenotypic features of the lymph node closely resemble ALK-negative ALCL, characterized by uniform CD30 expression and a subcapsular distribution of lymphoma cells. However, the lymphoma cells exhibit diffuse positivity for EBV, consistent with EBV+ NT/NKCL. A case of ALK-negative ALCL with an immunophenotype identical to the EBV-positive case is included for comparison. Given that EBV+ NT/NKCL represents an aggressive neoplasm requiring unique clinical management compared to ALK-negative ALCL, it is critical to accurately differentiate EBV+ NT/NKCL from ALK-negative ALCL with a cytotoxic T-cell immunophenotype.

RESUMEN

Epstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-γ), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-α) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-ß: TNF-α and TGF-ß: IFN-γ attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS.

Asunto(s)

Exosomas , Herpesvirus Humano 4 , MicroARNs , Esclerosis Múltiple Recurrente-Remitente , Humanos , Exosomas/metabolismo , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/virología , Herpesvirus Humano 4/genética , Femenino , Masculino , MicroARNs/líquido cefalorraquídeo , MicroARNs/genética , Adulto , Citocinas/líquido cefalorraquídeo , Infecciones por Virus de Epstein-Barr/líquido cefalorraquídeo , Infecciones por Virus de Epstein-Barr/virología , ARN Viral/líquido cefalorraquídeo , ARN Viral/genética , Persona de Mediana Edad , Interferón gamma/líquido cefalorraquídeo

RESUMEN

BACKGROUND: Shyonaka (Oroxylum indicum Vent) is widely used in Ayurveda and in ethnomedical practice for the treatment of inflammation, pain, diarrhea, non-healing ulcers, and cancer. Owing to the high prevalence of Epstein-Barr virus (EBV) infection in Nasopharyngeal carcinoma (NPC) patients, simultaneous targeting of proteins involved in both EBV replication and NPC proliferation might help to manage the disease effectively. OBJECTIVES: This study is designed to identify potential dual targeting inhibitors from Oroxylum indicum having the potential to inhibit both EBV and NPC. This study also attempted quantitative analysis of Shyonaka Bark Decoction (SBD) to confirm the presence of Baicalein and Chrysin which are predominant marker compounds of Shyonaka. METHODOLOGY: The HPLC analysis of stem bark and root bark of Oroxylum indicum was done to estimate the presence of marker compounds Baicalein and Chrysalin. The in-silico analysis included ADMET analysis followed by molecular docking of known compounds from Oroxylum indicum (retrieved from IMPPAT database) onto the target proteins of EBV (BHRF1, NEC1, dUTPase, Uracil DNA glycosylase) and NPC (COX-2, EGFR, and MDM2) using DOCK6 tool. Further validations were done using the molecular dynamics simulations of top screened molecules onto the selected target proteins using AMBER20 package and their corresponding MMGBSA binding free-energy values were calculated. RESULTS: The molecular docking revealed that the key molecules from the plant, scutellarein 7-rutinoside (S7R), scutellarin (SCU) and 6-hydroxyluteolin, Baicalein and 5,7-Dihydroxy-2-phenyl-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one (57D) are effectively intervening with the target proteins of EBV, one of the key causative factors of NPC and the NPC specific targets which have the potential to reduce tumor size and other consequences of NPC. The molecular dynamics simulations of S7R, Baicalein and 57D, Baicalein with MDM-2 protein and dUTPase protein, respectively, showed stable interactions between them which were further assessed by the binding energy calculations. CONCLUSION: Overall, the in-silico evaluation of these phytochemicals with target proteins indicates their potential to inhibit both EBV and NPC which needs further in-vitro and in-vivo validations.

Asunto(s)

Linfohistiocitosis Hemofagocítica , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/diagnóstico , Humanos , Animales

RESUMEN

BACKGROUND: Aberrant DNA methylation is a common epigenetic modification in cancers, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Therefore, the analysis of methylation levels appears necessary to improve cancer therapy and prognosis. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to analyse global DNA methylation levels in OPSCC and OSCC tumours and the margin samples after DNA isolation. HPV detection was conducted by hybridisation using GenoFlow HPV Array Test Kits (DiagCor Bioscience Inc., Hong Kong, China). EBV detection was performed using real-time PCR with an EBV PCR Kit (EBV/ISEX/100, GeneProof, Brno, Czech Republic). RESULTS: OPSCC tumour samples obtained from women showed lower global DNA methylation levels than those from men (1.3% vs. 3.5%, p = 0.049). The margin samples from OPSCC patients with HPV and EBV coinfection showed global DNA methylation lower than those without coinfection (p = 0.042). G3 tumours from OSCC patients had significantly lower levels of global DNA methylation than G2 tumours (0.98% ± 0.74% vs. 3.77% ± 4.97%, p = 0.010). Additionally, tumours from HPV-positive OSCC patients had significantly lower global DNA methylation levels than those from HPV-negative patients (p = 0.013). In the margin samples, we observed a significant negative correlation between global DNA methylation and the N stage of OSCC patients (rS = -0.33, p = 0.039). HPV-positive OPSCC patients had higher global DNA methylation levels than HPV-positive OSCC patients (p = 0.015). CONCLUSION: We confirmed that methylation could be changed in relation to viral factors, such as HPV and EBV, as well as clinical and demographical parameters.