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1.
Medicine (Baltimore) ; 99(1): e18503, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895784

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. In clinical practice, we have observed that some HLH patients who have features of systemic autoinflammatory diseases (SAIDs) exhibit unique clinical manifestations and outcomes different from other HLH patients.We analyzed data from 25 HLH patients who were considered to have SAIDs; data were collected from patients of our center between January 1, 2015 and September 1, 2018.The median age of the patients was 1.75 years. In the early phase, all patients had a fever and 92% of patients had a rash; 96% of patients had high white blood cell count (WBC), C-reaction protein, and erythrocyte sedimentation rate. With progression, the above laboratory results decreased gradually. During the HLH period, we compared SAIDs-related HLH and Epstein-Barr virus (EBV)-related HLH and found that rash was more common (92%, P < .001) and splenomegaly was less common (64%, P = .023) in SAIDs-related HLH. Further, WBC, ferritin, and Interleukin-6 levels in SAIDs-related HLH patients were higher than those in EBV-related HLH patients. In contrast, hemoglobin, triglyceride, sCD25, Interleukin-10, and interferon-γ levels in SAIDs-related HLH patients were lower compared with those in EBV-related HLH patients. SAIDs-related HLH patients received a modified HLH-2004 protocol at our center. Most patients had a good prognosis.We provide a summary of the unique clinical and laboratory features, treatment protocols, and outcomes of SAIDs patients with HLH at onset. The findings indicate that these patients had a better response to corticosteroids and cyclosporin compared with EBV-related HLH patients.


Assuntos
Doenças Autoimunes/patologia , Infecções por Vírus Epstein-Barr/patologia , Exantema/etiologia , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica/patologia , Corticosteroides/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , Sedimentação Sanguínea , Proteína C-Reativa , Ciclosporina/uso terapêutico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Exantema/patologia , Exantema/virologia , Feminino , Humanos , Lactente , Contagem de Leucócitos , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Esplenomegalia/imunologia , Esplenomegalia/virologia , Resultado do Tratamento
2.
Transplant Proc ; 51(9): 3163-3166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619339

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is caused by uncontrolled proliferation of lymphoid cells after a hematopoietic stem cell or solid organ transplant procedure related to the Epstein-Barr virus (EBV) infection. A primary central nervous system (CNS) PTLD (CNS-PTLD) is rare and important to distinguish from an intracranial lesion after transplantation. A 66-year-old man with pulmonary arterial hypertension who underwent living-donor lung transplantation 9 years prior noticed disorientation regarding route and dates. Brain magnetic resonance imaging revealed multiple white matter lesions and fluorodeoxyglucose (FDG) positron emission tomography showed FDG uptake in the brain and skin. CNS-PTLD was diagnosed by craniotomy biopsy and EBV-encoded RNA was positive in in situ hybridization findings and elevated in brain tissue. The treatment was started with immunosuppressant reduction and whole brain radiotherapy. But the condition progressed rapidly over 2 months after the first symptom and the patient was passed away 25 days after hospitalization. CNS-PTLD can occur several years after transplantation and it is necessary to keep in mind to distinguish brain disease because early diagnosis and treatment are important.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Pulmão , Transtornos Linfoproliferativos/imunologia , Complicações Pós-Operatórias/imunologia , Idoso , Encéfalo/patologia , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Masculino
3.
Isr Med Assoc J ; 21(7): 444-448, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507118

RESUMO

BACKGROUND: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed. OBJECTIVES: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential. METHODS: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases. RESULTS: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10). CONCLUSIONS: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.


Assuntos
Autoantígenos/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Peptídeos/imunologia , Proteoma , Complemento C4/imunologia , Reações Cruzadas/imunologia , Bases de Dados Factuais , Herpesvirus Humano 4/imunologia , Humanos , Interleucina-10/imunologia
4.
Int J Infect Dis ; 88: 31-33, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31398454

RESUMO

A 69-year-old man who underwent cord blood transplantation seven years ago was admitted because of fever, elevated liver enzymes and thrombocytopenia. Bone marrow aspirate revealed hemophagocytic lymphohistiocytosis. Viral capsid antigen (VCA)-immunoglobulin (Ig) G, VCA-IgM, VCA-IgA, Epstein-Barr virus nuclear antigen-IgG, early antigen-diffuse-type and restricted-type (EA-DR) IgG, and EA-DR IgA titers were 2560, <10, 10, 40, 40, and <10, respectively. Real-time polymerase chain reaction assay of peripheral whole blood for Epstein-Barr virus-deoxyribonucleic acid (EBV-DNA) revealed 240,000 copies/µg DNA. Flow cytometric in situ hybridization assay confirmed that EBV-infected cells were NK-cells. Clonality evaluation by Southern blot assay of EBV-DNA terminal repeats proved to be bi-clonal. Accordingly, we made a diagnosis of NK-cell post-transplant lymphoproliferative disease with chronic active EBV infection-like clinical findings (CAEBV-like NK-cell PTLD). Although CAEBV-like PTLD is extremely rare, its prognosis seems to be very poor. The disease should be considered in such patients who present persistent or recurrent infectious mononucleosis-like symptoms after transplantation.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/imunologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Idoso , Doença Crônica , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Humanos , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Masculino , Prognóstico
5.
Eur Arch Otorhinolaryngol ; 276(11): 3131-3138, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31456038

RESUMO

OBJECTIVE: We investigated the correlation between the expression of IL-17A in nasopharyngeal carcinoma tissues and cells and the occurrence and development of NPC was also investigated. METHODS: Forty-five NPC biopsy specimens from January 2014 to January 2016 were selected. Forty-five NPC tissue specimens and 45 chronic nasopharyngitis tissue samples were detected by immunohistochemistry. Statistical methods were used to analyze the correlation between IL-17A expression and the clinicopathological variables of NPC. The NPC patients were followed up. The levels of IL-17A mRNA in 40 NPC tissue specimens and 45 chronic nasopharyngitis tissue samples were detected by real-time PCR. IL-17A expression in 15 NPC tissue specimens and chronic nasopharyngitis tissue samples was further detected by Western blotting assays. RESULTS: IL-17A expression in NPC tissues was significantly higher than that of chronic nasopharyngitis tissues (P < 0.05). IL-17A was expressed in the nucleus and cytoplasm of both NPC tissues and chronic nasopharyngitis tissues. Stage III + IV NPC, tumor volume ≥ 50 mm, and hepatic envelope invasion and cervical lymph node metastasis were associated with significantly higher IL-17A levels versus stage I + II NPC, tumor size < 50 mm, no membrane invasion and lack of cervical lymph node metastasis (P < 0.05). IL-17A was statistically associated with tissue differentiation, serum EBV-lgA levels, and EBV infection. IL-17A-positive patients had significantly longer median survival versus IL-17A-negative patients (21.0 vs. 13.0 months, log-rank test: P < 0.05). Furthermore, 65% (26/40) of NPC tissue samples had significantly higher IL-17A mRNA levels than chronic nasopharyngitis (P < 0.05). IL-17A expression was significantly higher in NPC ≥ 50 mm, stage III + IV NPC and NPC with cervical lymph node invasion than its corresponding chronic nasopharyngitis tissue. CONCLUSION: IL-17A may be involved in the regulation of various malignant biological behaviors of NPC, which is closely related to the occurrence and development of NPC.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Interleucina-17/metabolismo , Linfonodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adulto , Correlação de Dados , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/imunologia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Nasofaringite/imunologia , Estadiamento de Neoplasias
6.
J Clin Neurosci ; 69: 269-272, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31451379

RESUMO

Lymphomas affecting the central nervous system (CNS), both primarily and secondarily, are uncommon malignancies. Immunosuppressed states, including iatrogenic immunosuppression following organ transplantation, are the most significant risk factors for developing primary CNS lymphoma (PCNSL). Post-transplant lymphoproliferative disease (PTLD) is a well described complication following bone marrow or solid organ transplantation. PTLD is usually a systemic disease with occasional CNS involvement. The incidence of CNS involvement in PTLD is low, and the majority of these cases tend to be PCNSL. Hodgkin lymphoma PTLD (HL-PTLD) constitutes only a very small percentage of PTLD. We report a rare case of a primary intraventricular CNS classical HL-PTLD in a male patient, 18 years following renal transplantation. The location allowed for safe neurosurgical intervention which resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. Both the ventricular location of the PTLD and Hodgkin Lymphoma PTLD are themselves individually quite rare and have not previously been reported together. The unique location allowed safe neurosurgical intervention which quickly resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen.


Assuntos
Neoplasias do Ventrículo Cerebral/imunologia , Doença de Hodgkin/imunologia , Hospedeiro Imunocomprometido , Transplante de Rim , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Cancer Immunol Immunother ; 68(8): 1317-1329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31312900

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an EBV-associated neoplasm occurring endemically in Southeast Asia and sporadically all over the world. In children and adolescents, high cure rates have been obtained using chemotherapy, radiochemotherapy and maintenance therapy with interferon beta (IFNß). The mechanism by which IFNß contributes to a low systemic relapse rate has not yet been fully revealed. PATIENTS AND METHODS: NK cells and serum samples from two patients with NPC were analyzed before and at different time points during IFNß therapy, for assessment of TRAIL expression and NK cell cytotoxicity. Cytotoxicity was measured using the calcein release assay and the contribution of different death effector pathways was analyzed using specific inhibitors. RESULTS: Treatment with IFNß induced TRAIL expression on patients' NK cells and increased their cytotoxicity against NPC targets in vitro. NK cell-mediated cytotoxicity was predominately mediated via TRAIL. IFNß also induced the production of soluble TRAIL (sTRAIL) by NK cells and its release upon contact with NPC cells. IFNß treatment increased serum levels of sTRAIL in patients. Moreover, sTRAIL concentrated from patients' serum samples induced apoptosis ex vivo in NPC cells from a patient-derived xenograft. CONCLUSION: Increased cytotoxicity of NK cells against NPC cells and increased serum levels of biologically active TRAIL in patients treated with IFNß could be a means to eliminate micrometastatic disease and explain the low systemic relapse rate in this patient group.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/fisiologia , Imunoterapia/métodos , Interferon beta/uso terapêutico , Células Matadoras Naturais/imunologia , Carcinoma Nasofaríngeo/terapia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Adolescente , Animais , Apoptose , Linhagem Celular Tumoral , Criança , Citotoxicidade Imunológica , Feminino , Humanos , Camundongos , Camundongos Nus , Carcinoma Nasofaríngeo/imunologia , Recidiva Local de Neoplasia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Georgian Med News ; (290): 69-73, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322518

RESUMO

Epstein-Barr virus (EBV) is referred to the viruses with lifelong persistence in the human body in active and latent phases. EBV initiates impairment of expression of cell microRNA, which participates in the regulation of immune system function and can be related to different pathological conditions, including allergopathy. Aim - to assess the levels of miR-146a and miR-155 expression in patients with allergopathy in combination with active and latent phases of EBV infection. Clinical, general laboratory, cytological, instrumental, specific allergological, molecular-genetic investigations were performed. Based on these investigations, patients were divided into two groups: 1st group (27 individuals) with allergopathy and active phase of chronic EBV-infection, 2nd group (19 individuals) with allergopathy and latent phase of EBV infection. Control group included 20 healthy individuals. Higher (р>0.05) levels of miR-146a expression were detected in patients of both groups compared with control group. Expression of miR-155 was higher (р>0.05) only in patients of the 1st group compared with control. No significant difference was noticed between investigated groups. In latent phase, EBV uses own mechanisms of latency to avoid immune surveillance, which are manifested by increase in miR-155 and miR-146а expression. In active phase, this vector of changes intensified and was associated with acute manifestations of allergopathy.


Assuntos
Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/metabolismo , Hipersensibilidade/imunologia , MicroRNAs/genética , Adolescente , Adulto , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Latência Viral , Adulto Jovem
9.
Georgian Med News ; (289): 158-162, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31215899

RESUMO

Epstein-Barr virus (EBV) initiates various immune disorders, including changes in cytokine profile, which result in the development of different pathological conditions, in particular, allergopathology. Aim - to investigate the level of cytokines with antiviral activity in patients with allergopathology in active and latent phases of chronic persistence of Epstein-Barr viral infection. In general, 38 patients with allergopathology in combination with chronic persistence of EBV-infection in active (1st group) and latent (2nd group) phases were examined. A complex clinical and laboratory examination was performed; immunological, molecular and genetic, instrumental investigations, statistical analysis of the results were conducted. Peculiarities of the levels of cytokines with antiviral activity IL12, IL1ß, IL33, TNF-α, IFN-g were investigated in two groups of patients: 1st group - patients with allergy in combination with active phase (PCR "+") of chronic EBV infection, 2nd group - patients with allergy in combination with latent phase (PCR "-") of chronic EBV infection. Control group - 20 healthy individuals of corresponding gender and age. In patients with allergopathology in combination with chronic persistence of EBV, marked deregulation of optimal correlation of cytokine network components was detected, in particular, elevation of IL1ß concentration with simultaneous decrease in IL12, IL33 and normal level of IFN-g and TNF-α (in active phase) and reduction of IL1ß, IFN-g concentration with simultaneous increase in IL12, IL33 and normal level of TNF-α (in latent phase) of infection. Absence of consolidated influence of investigated cytokines with antiviral activity plays a leading role in pathogenesis of pathological process under conditions of continuous persistence of the virus in the body with its further activation. The obtained proofs of cytokine imbalance indicate inadequate cell-mediated and humoral response of the body in chronic EBV-infection with allergopathology formation.


Assuntos
Antivirais , Infecções por Vírus Epstein-Barr , Antivirais/uso terapêutico , Citocinas , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4 , Humanos , Fator de Necrose Tumoral alfa
10.
Clin Lab ; 65(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232014

RESUMO

BACKGROUND: Previous research showed that virus infection is correlated with the occurrence, development, and prognosis of AA. This study was designed to explore the influence of virus infection on the immune functionality and immunosuppressive therapy (IST) efficiency of newly diagnosed SAA patients. METHODS: Fifty-six newly diagnosed SAA patients combined with virus infection treated in the Hematology Department of Tianjin Medical University General Hospital from October 2004 to July 2014 were studied. Various immune parameters were tested and compared for SAA patients with and without virus infection. RESULTS: When compared with SAA patients without corresponding virus infection, SAA patients with CMV-IgM, PVB19-IgM, and EBV infection had increased CD8+ T cell percentage, decreased CD4+/CD8+ T cell ratios, and increased CD8+HLA-DR+/CD8+ percentage. The absolute value of CD8+ T cell of CMV-IgM group had increased as well. The CMV-IgM and PVB19-IgM groups showed decreased CD4+ T cell percentage, and decreased CD4+HLA-DR+/CD8+HLA-DR+ ratio. The PVB19-IgM group exhibited decreased CD4+HLA-DR+/CD4+ percentage, increased Th1 percentage and increased pDC percentage. Patients with EB virus infection showed lower NK cell percentage. Three years after IST, the treatment is significantly less effective for the SAA patients combined with virus infection than those without. CONCLUSIONS: CMV, PVB19, and EBV infection worsen the immune functionality abnormality of newly diagnosed SAA patients and reduce the IST efficiency.


Assuntos
Anemia Aplástica/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Antígenos HLA-DR/imunologia , Viroses/imunologia , Adolescente , Adulto , Idoso , Anemia Aplástica/complicações , Anemia Aplástica/terapia , Relação CD4-CD8 , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Viroses/complicações , Viroses/virologia , Adulto Jovem
11.
Blood ; 133(26): 2753-2764, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31064750

RESUMO

Patients with classic hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that whites were less likely to develop systemic EBV disease (1/10) than nonwhites (5/6). All (10/10) of the white patients were generally in good health at last follow-up, while two-thirds (4/6) of the nonwhite patients required hematopoietic stem cell transplantation. Nonwhite patients had later age of onset of HVLPD than white patients (median age, 8 vs 5 years) and higher levels of EBV DNA (median, 1 515 000 vs 250 000 copies/ml) and more often had low numbers of NK cells (83% vs 50% of patients) and T-cell clones in the blood (83% vs 30% of patients). RNA-sequencing analysis of an HVLPD skin lesion in a white patient compared with his normal skin showed increased expression of interferon-γ and chemokines that attract T cells and NK cells. Thus, white patients with HVLPD were less likely to have systemic disease with EBV and had a much better prognosis than nonwhite patients. This trial was registered at www.clinicaltrials.gov as #NCT00369421 and #NCT00032513.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Hidroa Vaciniforme/virologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/etnologia , Infecções por Vírus Epstein-Barr/imunologia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Transtornos Linfoproliferativos/etnologia , Masculino
12.
Medicine (Baltimore) ; 98(18): e15329, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045771

RESUMO

RATIONALE: Gain of function (GOF) mutations in PIK3CD gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, cytomegalovirus and/or epstein-Barr virus (EBV) viremia, and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. PATIENT CONCERNS: We report a patient who was diagnosed with systemic lupus erythematosus (SLE) at a young age and was recently found to carry heterozygous mutations in PIK3CD. The patient not only presented with recurrent sinopulmonary infections, CD4 lymphopenia, lymphadenopathy, EBV viremia, and elevated serum IgM, but also met classification criteria of SLE based on persistent proteinuria and hematuria, leukopenia and anemia, low level of serum complement, and positive autoantibody for antinuclear antibodies. DIAGNOSES: Activated PI3Kδ syndrome. INTERVENTIONS: Oral prednisolone and hydroxychloroquine combined with mycophenolate mofetil was given to the patient. He was currently receiving intravenous immunoglobulin per month in association with hydroxychloroquine, low-dose prednisolone, and mycophenolate mofetil. OUTCOMES: At present, the level of complement restored to normal, hematuria and proteinuria disappeared, and liver function returned to normal. LESSONS: SLE may be a novel phenotype of GOF mutation in PI3CKD gene (GOF PIK3CD).


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação com Ganho de Função/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Lúpus Eritematoso Sistêmico/genética , Adolescente , Anticorpos Antinucleares/sangue , Grupo com Ancestrais do Continente Asiático/genética , Classe I de Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Proteínas do Sistema Complemento/análise , Proteínas do Sistema Complemento/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/imunologia , Glucocorticoides/uso terapêutico , Herpesvirus Humano 4/imunologia , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Fenótipo , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico
13.
BMC Infect Dis ; 19(1): 404, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077135

RESUMO

BACKGROUND: Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab. CASE PRESENTATION: An 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn's disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16 years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4 weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30 days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8 weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90 days after the cessation of azathioprine. CONCLUSIONS: We found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3 months after the stopping of azathioprine, coincided with the clearance of viremia and clinical recovery. Finally, our choice of treating the patient with rituximab, as previously used for patients with a severe immunosuppression and Epstein-Barr virus viremia, appeared to be successful in this case. We suggest testing for Epstein-Barr virus serology before starting azathioprine and measuring natural killer cell counts during the treatment to identify patients at risk of developing an unusually severe primary Epstein-Barr virus infection.


Assuntos
Azatioprina/efeitos adversos , Infecções por Vírus Epstein-Barr/etiologia , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/complicações , Células Matadoras Naturais , Azatioprina/uso terapêutico , Biópsia , Criança , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Contagem de Linfócitos , Estudos Prospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
14.
Zhonghua Yan Ke Za Zhi ; 55(5): 374-380, 2019 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-31137150

RESUMO

Objective: To evaluate the clinicopathological features of ocular natural killer(NK)/T cell lymphoma. Methods: Data of 21 patients (22 eyes) with ocular NK/T cell lymphoma treated at Eye & ENT Hospital of Fudan University from January 2006 to March 2018 were retrospectively analyzed for clinical data, morphology, immunophenotype and outcomes. Results: There were 10 males and 11 females with ages from 3 to 77 years (mean, 43 years). There were 20 unilateral cases (10 left eyes and 10 right eyes) and 1 bilateral case. Except for 1 case of corneal perforation resulting from the involvement of the conjunctiva and cornea, the other cases all involved the orbit (including eyelids and conjunctiva) as demonstrated by radiologic studies, with the lacrimal sac involved in 3 cases, and the nasal cavity or maxillary sinus involved in 2 cases. Three patients had been previously diagnosed sinonasal NK/T cell lymphoma with radiotherapy and chemotherapy. Two patients had a history of ovarian NK/T cell lymphoma with chemotherapy. One patient had multiple ulcers of skin and mucosa at presentation. There were 13 primary ocular NK/T cell lymphomas without evidence of nasal or systemic involvement. All patients presented with eyelid swelling and decreased visual acuity. There were proptosis in 18 cases, motility restriction in 13 cases, eyelid ulceration in 3 cases, and fever in 4 cases. They had all been previously diagnosed as orbital pseudotumor or cellulitis and there was no response to steroids and antibiotics. Pathological examination showed atypical lymphoid infiltration with an angioinvasive growth pattern causing coagulative necrosis. Cytologically, the medium-sized neoplastic cells showed irregular folded nuclei. The neoplastic cells were positive for cytoplasmic CD3ε, CD56, and cytotoxic molecules and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization. Seven patients were lost to follow-up. Ten patients died 2.0 to 17.0 months after diagnosis (mean, 6.3 months) despite treatment with chemotherapy and radiotherapy. Conclusions: Ocular NK/T cell lymphoma is a rare form of ocular lymphoma. There are primary NK/T cell lymphoma and secondary ocular NK/T cell lymphoma with nasal or systemic involvement. The rarity of this tumor and inflammatory signs make it challenging to identify these tumors early. The neoplastic cells are positive for cytoplasmic CD3ε, CD56, cytotoxic molecules and EBER in situ hybridization. Despite aggressive therapy, it demonstrates high lethality with poor prognosis. (Chin J Ophthalmol, 2019, 55: 374-380).


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Neoplasias Oculares/patologia , Células Matadoras Naturais/patologia , Linfoma de Células B , Linfoma de Células T/patologia , Neoplasias Orbitárias/patologia , Neoplasias Cutâneas/patologia , Linfócitos T/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/imunologia , Neoplasias Oculares/imunologia , Neoplasias Oculares/terapia , Neoplasias Oculares/virologia , Feminino , Humanos , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/virologia , Resultado do Tratamento , Adulto Jovem
15.
Scand J Immunol ; 90(4): e12796, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31145476

RESUMO

Nasopharyngeal carcinoma (NPC) is one the most confusing and rare malignancy in most part of the world with significantly high occurrence in some populations of Southeast Asia, North Africa and Alaska. Apart from the dietary and environmental factors, NPC is well-associated with Epstein-Barr virus (EBV) infection in these ethnic groups. However, the internal molecular mechanism(s) for such association in specific populations is not known till date. Polymorphisms in the genes of histocompatibility locus antigens (HLA) are reported in NPC, but association of any particular polymorphism with ethnicity is not established yet. Here, we report a set of HLA polymorphisms in EBV-infected NPC samples from Northeast Indian population. These polymorphisms might play an important role for the lack of proper immune function against EBV infection and thus, eventually, for NPC generation in endemic populations like those of Northeast India.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Grupos Étnicos , Genótipo , Antígenos HLA/genética , Herpesvirus Humano 4/fisiologia , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Viés , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/genética , Frequência do Gene , Predisposição Genética para Doença , Histocompatibilidade/genética , Humanos , Imunidade/genética , Índia/epidemiologia , Índia/etnologia , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético
16.
PLoS Pathog ; 15(5): e1007748, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31145756

RESUMO

Epstein Barr virus (EBV) is one of the most ubiquitous human pathogens in the world, persistently infecting more than 90% of the adult human population. It drives some of the strongest human CD8+ T cell responses, which can be observed during symptomatic primary infection known as infectious mononucleosis (IM). Despite high viral loads and prolonged CD8+ T cell stimulation during IM, EBV enters latency and is under lifelong immune control in most individuals that experience this disease. We investigated whether changes in T cell function, as frequently characterized by PD-1 up-regulation, occur during IM due to the prolonged exposure to high antigen levels. We readily detected the expansion of PD-1 positive CD8+ T cells together with high frequencies of Tim-3, 2B4, and KLRG1 expression during IM and in mice with reconstituted human immune system components (huNSG mice) that had been infected with a high dose of EBV. These PD-1 positive CD8+ T cells, however, retained proliferation, cytokine production, and cytotoxic abilities. Multiple subsets of CD8+ T cells expanded during EBV infection, including PD-1+Tim-3+KLRG1+ cells that express CXCR5 and TCF-1 germinal center homing and memory markers, and may also contain BATF3. Moreover, blocking the PD-1 axis compromised EBV specific immune control and resulted in virus-associated lymphomagenesis. Finally, PD-1+, Tim-3+, and KLRG1+ CD8+ T cell expansion coincided with declining viral loads during low dose EBV infection. These findings suggest that EBV infection primes PD-1 positive CD8+ T cell populations that rely on this receptor axis for the efficient immune control of this ubiquitous human tumor virus.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Citotóxicos/imunologia , Carga Viral/imunologia , Adulto , Animais , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Estudos de Casos e Controles , Citocinas/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Perfilação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID
17.
Eur J Dermatol ; 29(1): 21-28, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998212

RESUMO

Hydroa vacciniforme (HV) is a cutaneous subset of Epstein-Barr virus (EBV)-associated T/NK lymphoproliferative disorders (LPDs). Our previous case series study clearly showed a clinical spectrum of EBV-associated T/NK LPDs including HV, hypersensitivity to mosquito bites (HMB), chronic active EBV infection (CAEBV), and hemophagocytic lymphohistiocytosis (HLH). Patients with HV are divided into two groups: a benign subtype designated "classic HV" (cHV) and more serious systemic HV (sHV), also called "HV-like LPD" in the 2017 World Health Organization (WHO) classification. Patients with cHV usually have an increased number of EBV-infected γδT cells and patients with sHV without HMB are further classified into two groups: γδT-cell- and αßT-cell-dominant types. Patients with HMB, with or without HV-like eruptions, have an increased number of EBV-infected NK cells in the blood. Patients with cHV and γδT-cell-dominant sHV show a favourable prognosis, but the other subtypes such as αßT-cell-dominant sHV and HMB have a poor prognosis with mortality rates of 11.5 and 3.51 per 100 person-years, respectively. In addition to the clinical subtypes and the dominant lymphocyte subsets, the poor prognostic indicators include onset age over nine years and expression of the reactivation marker, BZLF1 mRNA. No prognostic correlation has been reported for anti-EBV antibody titres or EBV DNA load. The clinical subtypes and their prognostic factors should be considered for therapeutic interventions.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Hidroa Vaciniforme/imunologia , Hidroa Vaciniforme/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Dermatopatias Virais/imunologia , Dermatopatias Virais/virologia , Humanos
18.
Immunity ; 50(5): 1305-1316.e6, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30979688

RESUMO

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/gL and gp42 contributed to B cell neutralization. Immunization of mice and nonhuman primates with nanoparticle vaccines that displayed components of the viral-fusion machinery EBV gH/gL or gH/gL/gp42 elicited antibodies that potently neutralized both epithelial-cell and B cell infection. Immune serum from nonhuman primates inhibited EBV-glycoprotein-mediated fusion of epithelial cells and B cells and targeted an epitope critical for virus-cell fusion. Therefore, unlike the leading EBV gp350 vaccine candidate, which only protects B cells from infection, these EBV nanoparticle vaccines elicit antibodies that inhibit the virus-fusion apparatus and provide cell-type-independent protection from virus infection.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Células Epiteliais/imunologia , Infecções por Vírus Epstein-Barr/prevenção & controle , Herpesvirus Humano 4/imunologia , Glicoproteínas de Membrana/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Linfócitos B/virologia , Células CHO , Fusão Celular , Linhagem Celular Tumoral , Cricetulus , Células Epiteliais/virologia , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Células HEK293 , Células HeLa , Humanos , Soros Imunes/administração & dosagem , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/imunologia , Ligação Viral
19.
J Cutan Pathol ; 46(9): 637-644, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30980412

RESUMO

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL) is a systemic peripheral T-cell lymphoma with a follicular helper T-cell (TFH ) immunophenotype that frequently involves the skin. However, the histopathology of cutaneous involvement by AITL has not been fully established. METHODS: We reviewed the clinicopathological features of 19 patients seen at our institution with AITL involving the skin. Pan-T-cell and TFH marker expression was evaluated by immunohistochemistry. Epstein-Barr virus (EBV) was detected using in situ hybridization (ISH) for Epstein-Barr virus-encoded small RNA (EBER). T-cell receptor (TCR) gene rearrangement was evaluated by PCR. RESULTS: AITL affected both trunk and extremities in 15/19 cases (79%). Perivascular infiltration by small and/or medium-sized lymphocytes was seen in 18/19 (95%). Granulomatous inflammation was identified in 4/19 (21%). Aberrant loss of CD2, CD5, or CD7 was identified in 1/18 (6%), 2/18 (11%), or 7/19 (37%) cases, respectively. Seventeen of eighteen evaluable cases (95%) expressed 2 to 3 TFH markers: PD-1 in 19/19 (100%), BCL6 in 94% (17/18), and CD10 in 37% (7/19). EBV-positive cells were detected in 3/18 (17%) with varying density. Clonal TCR gene rearrangement was identified in 9/11 (82%). CONCLUSIONS: Cutaneous involvement by AITL shows relatively non-specific histopathological features. However, an immunohistochemical panel including TFH markers and EBER ISH is useful in differential diagnosis.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4/imunologia , Linfoma Cutâneo de Células T , Linfoma de Células T Periférico , Neoplasias Cutâneas , Linfócitos T Auxiliares-Indutores , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Imunofenotipagem , Linfoma Cutâneo de Células T/imunologia , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/virologia , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Auxiliares-Indutores/virologia
20.
Clin Lab ; 65(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969068

RESUMO

BACKGROUND: The aim of this study was to prove the difference between 37°C water incubation method and the BEP III automated immunoassay analyzer incubation method in anti-EBNA1-IgA antibody detection and to find the best way to improve the consistency of the two incubation methods. METHODS: The 37°C water incubation method and BEP III analyzer incubation method were used with the same panel of samples (n = 39) in anti-EBNA1-IgA antibody detection. Except for incubation, the rest of the steps were performed by the BEP III analyzer in both groups. All the data were analyzed by SPSS 17.0 software. Line charts and bar charts were used to compare the difference between the two incubation methods in anti-EBNA1-IgA antibody detection. We planned to find the best incubation scheme for BEP III analyzer, consistent with the water incubation method, using three groups of prolonged incubation time experiments. RESULTS: A sample panel of 39 outpatients were analyzed by two incubation methods. The results showed by line charts that the water incubation method had higher S/CO values than the BEP III analyzer incubation method. Meanwhile the water incubation group had more positive results (61.5%) and less borderline positive results (35.9%) than that of the BEP III analyzer incubation group which were 43.5% and 51.2%, respectively, in the stacked bar charts. We found that by prolonging the incubation time in the BEP III analyzer for 6 minutes in the first and second incubation steps the S/CO values we increased and achieved statistically coincident results with water incubation group. CONCLUSIONS: There were biases between the 37°C water incubation method and the BEP III analyzer incubation method in anti-EBNA1-IgA antibody detection. The water incubation method had higher S/CO values than the BEP III analyzer incubation method in paired groups and led partly to a difference in test results. By prolonging the BEP III analyzer incubation time properly, it can reduce the difference to some extent resulting in statistically similar results with the water incubation method.


Assuntos
Anticorpos Antivirais/isolamento & purificação , Infecções por Vírus Epstein-Barr/imunologia , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Imunoensaio/métodos , Imunoglobulina A/isolamento & purificação , Antígenos Virais/imunologia , Automação , Proteínas do Capsídeo/imunologia , Ensaio de Imunoadsorção Enzimática , Herpesvirus Humano 4/imunologia , Humanos , Pacientes Ambulatoriais , Controle de Qualidade , Reprodutibilidade dos Testes , Manejo de Espécimes
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