Asunto(s)

Proteínas ADAM/genética , Enfermedades Genéticas Congénitas , Mutación de Línea Germinal , Enfermedades Renales , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica , Proteína ADAMTS13 , Adolescente , Adulto , Femenino , Enfermedades Genéticas Congénitas/enzimología , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/fisiopatología , Enfermedades Genéticas Congénitas/terapia , Humanos , Riñón/enzimología , Riñón/fisiopatología , Enfermedades Renales/enzimología , Enfermedades Renales/genética , Enfermedades Renales/fisiopatología , Enfermedades Renales/prevención & control , Masculino , Púrpura Trombocitopénica Trombótica/enzimología , Púrpura Trombocitopénica Trombótica/genética , Púrpura Trombocitopénica Trombótica/fisiopatología , Púrpura Trombocitopénica Trombótica/terapia

RESUMEN

This study aimed to assess the outcome of cardiovascular diseases for patients with chronic active Epstein-Barr virus infection (CAEBV). The study enrolled 15 patients (7 boys and 8 girls) who fulfilled the diagnostic criteria for CAEBV, including 10 patients with T-cell type and 3 patients with natural killer (NK)-cell type. The median age at the CAEBV onset was 6.3 years (range, 1.2-17.8 years). Regular cardiologic studies were performed during the median follow-up period of 8 years (range, 2-20 years). Nine patients (60%) had cardiac diseases including coronary artery lesion (CAL) (n = 4, 44%), decreased left ventricular ejection fraction and pericardial effusion in (n = 3, 33%), complete atrioventricular block (n = 1), and sudden arrest (n = 1). The frequency of fever (78%, p = 0.04) or cytopenias (100%, p = 0.01), as the major symptom among patients with cardiac complications, was higher than among those without complications. The median time from disease onset to detection of CAL was 3.4 years (range, 1.8-8.6 years). The mean z-score increased to 3.98. Seven patients (78%) with cardiac complications died of disease progression, hematopoietic stem cell transplantation-related events, or both. In two patients, CAL regressed after allogeneic cord blood transplantation. Among CAEBV patients, CAL was the most common cardiac complication and could not be controlled without the eradication of EBV-infected T- and NK-cells.

Asunto(s)

Enfermedades Cardiovasculares/etiología , Infecciones por Virus de Epstein-Barr/complicaciones , Adolescente , Anticuerpos Antivirales/análisis , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Niño , Preescolar , Enfermedad Crónica , ADN Viral/análisis , Diagnóstico Diferencial , Técnicas de Diagnóstico Cardiovascular , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Estudios de Seguimiento , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Humanos , Incidencia , Lactante , Japón/epidemiología , Masculino , Estudios Retrospectivos

RESUMEN

Chronic active Epstein-Barr virus (EBV) infection is a rare chronic mononucleosis syndrome involving clonally proliferating EBV-infected T-/NK-cells. EBV DNA was quantified in nonpleocytotic cerebrospinal fluid (CSF) of 9 patients. Three patients with neurologic and/or neuroimaging abnormalities showed high CSF copy numbers. In 1 patient, CSF copy number exceeded the peripheral blood value. CSF EBV-load may predict the central nervous system involvement of EBVT-/NK-cells.

Asunto(s)

Líquido Cefalorraquídeo/virología , Herpesvirus Humano 4/fisiología , Mononucleosis Infecciosa/virología , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Femenino , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Mononucleosis Infecciosa/líquido cefalorraquídeo , Células Asesinas Naturales , Imagen por Resonancia Magnética , Masculino , Reacción en Cadena de la Polimerasa , Linfocitos T , Carga Viral

RESUMEN

Neurologic complications, including meningoencephalitis, transverse myelitis, and peripheral neuropathy, have been reported in patients with acute infectious mononucleosis. Chronic active Epstein-Barr virus and human immunodeficiency virus infections occasionally induce central nervous system lymphoma. On the other hand, central nervous system disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. A 15-year-old girl who developed acute disseminated encephalomyelitis-like disease presenting fever, anuresis, diplopia, and muscle weakness is described here. Clinical and neuroimaging studies led to the diagnosis of encephalomyelitis. Despite the absence of infectious mononucleosis-like symptoms, anti-Epstein-Barr virus antibody titers in serum and cerebrospinal fluid showed the virus reactivation. The copy number of Epstein-Barr virus DNA increased in cerebrospinal fluid but not in peripheral blood. Ganciclovir and repeated methyl-prednisolone pulse therapy resulted in complete resolution. Central nervous system disease on the limited intrathecal reactivation of Epstein-Barr virus in immunocompetent children should be differentiated from acute disseminated encephalomyelitis.

Asunto(s)

Encefalitis Viral/virología , Herpesvirus Humano 4/fisiología , Mononucleosis Infecciosa/complicaciones , Mononucleosis Infecciosa/virología , Meningitis Viral/virología , Replicación Viral/fisiología , Adolescente , Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Encéfalo/patología , Encéfalo/fisiopatología , Encéfalo/virología , ADN Viral/análisis , Encefalitis Viral/inmunología , Encefalitis Viral/fisiopatología , Femenino , Dosificación de Gen/genética , Humanos , Inmunocompetencia/inmunología , Imagen por Resonancia Magnética , Meninges/patología , Meninges/fisiopatología , Meninges/virología , Meningitis Viral/inmunología , Meningitis Viral/fisiopatología , Médula Espinal/patología , Médula Espinal/fisiopatología , Médula Espinal/virología , Espacio Subaracnoideo/patología , Espacio Subaracnoideo/fisiopatología , Espacio Subaracnoideo/virología , Resultado del Tratamiento , Carga Viral

RESUMEN

Regular self-infusion of an activated prothrombin complex concentrate (APCC) has been successfully introduced to a 14-year-old boy with hemophilia A. The child was diagnosed as a neonate, and at age 7 years, developed a high titer (127 BU/mL) factor VIII inhibitor coincident with a protracted ankle joint bleeding. From age 7-10 years, he received on-demand therapy using a prothrombin complex concentrate (PCC), PROPLEX-ST. From age 10-14 years, he received prophylaxis with PROPLEX-ST, initiated after an intracranial hemorrhage and coincident anamnestic inhibitor response. Throughout 7-year period of PCC treatment, he experienced recurrent bleeding episodes. Self-prophylaxis with APCC, FEIBA VH [Anti-inhibitor Coagulant Complex] (50 U/kg/dose three times per week) using infusion pump was initiated at 14 years of age and has continued for 2 years. There were no bleeding, thrombotic events or other adverse events after initiation of this prophylaxis, and inhibitor levels decreased to 1 BU/mL. His quality of life was improved, particularly with respect to school. Our long observation proposes a well-disciplined home-based FEIBA prophylaxis in inhibitor-positive hemophiliacs.

Asunto(s)

Inhibidores de Factor de Coagulación Sanguínea , Factores de Coagulación Sanguínea/administración & dosificación , Hemorragia/prevención & control , Artropatías/prevención & control , Trombosis/prevención & control , Adolescente , Pueblo Asiatico , Inhibidores de Factor de Coagulación Sanguínea/sangre , Hemofilia A/sangre , Hemofilia A/complicaciones , Hemorragia/etiología , Humanos , Japón , Artropatías/etiología , Masculino , Autoadministración , Trombosis/etiología

RESUMEN

UNLABELLED: A 7-y-old girl presented with prolonged fever, arrhythmia and cardiomegaly during the treatment course of group A beta-haemolytic streptococcal pharyngitis. The isolated rheumatogenic strain M1 suggested the diagnosis of rheumatic fever. However, serous pericardial effusion contained high levels of Epstein-Barr virus (EBV) DNA. Clonally proliferating EBV+ T cells were determined in the circulation. The atypical carditis without valvitis was then complicated by coronary artery dilatations. Four months after the start of prednisolone plus antiviral/bacterial therapy, EBV+ T-cell lymphoma developed in the thigh. CONCLUSION: Atypical carditis may be a notable and life-threatening presentation of chronic active EBV infection to be differentiated from rheumatic fever.

Asunto(s)

Infecciones por Virus de Epstein-Barr/diagnóstico , Miocarditis/microbiología , Miocarditis/virología , Cardiopatía Reumática/diagnóstico , Niño , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Humanos , Miocarditis/diagnóstico

RESUMEN

Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia occasionally presenting physical anomalies. Ribosomal protein S19 gene (RPS19) is one of the causative genes for DBA; however, the pathologic mechanism of erythroblastopenia and abnormal morphology has not been clarified. To assess the pathophysiology of DBA, the gene expression profile of 2 representative patients carrying no RPS19 mutations was compared with that of aplastic anemia (AA) patients, assessed by the microarray analyses. The K-mean clustering analysis revealed the significant categorization of 28 ribosomal protein (RP) genes into a small set of group (994 genes) (P=2.39E-17), all of which were expressed at lower levels in DBA than in AA patients. RPS19 was categorized into the set of low expressing genes in DBA patients. No mutations were determined in the promoter and coding sequences of top 10 RP genes expressed at the levels over 1.2 of the AA/DBA ratio, in 3 DBA patients. These results indicated that the lower expression of RP gene group, even without the mutation, was a distinctive feature of DBA from AA, although the study number was small. The reduced RP gene expression, by itself, may suggest an underlying mechanism of the constitutional anemia.

Asunto(s)

Anemia de Diamond-Blackfan/metabolismo , Regulación de la Expresión Génica , Proteínas Ribosómicas/biosíntesis , Adulto , Anemia de Diamond-Blackfan/genética , Niño , Preescolar , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Ribosómicas/genética

RESUMEN

We describe 2 siblings who had interleukin-1 receptor-associated kinase 4 deficiency with a novel mutation in exon 2. They had delayed separation of the umbilical cord. The flow cytometric analysis of monocytic intracellular tumor necrosis factor-alpha production in response to lipopolysaccharide may be a useful method to screen for the disease.

Asunto(s)

Citometría de Flujo , Síndromes de Inmunodeficiencia/diagnóstico , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Proteínas Serina-Treonina Quinasas/deficiencia , Factor de Necrosis Tumoral alfa/metabolismo , Cordón Umbilical , Biomarcadores/metabolismo , Estudios de Casos y Controles , Preescolar , Exones/genética , Homocigoto , Humanos , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/genética , Quinasas Asociadas a Receptores de Interleucina-1 , Péptidos y Proteínas de Señalización Intracelular/genética , Lipopolisacáridos , Masculino , Análisis por Apareamiento , Monocitos/metabolismo , Mutación , Proteínas Serina-Treonina Quinasas/genética , Ácidos Teicoicos

RESUMEN

Treatment of severe aplastic anemia (SAA) patients who lack human leukocyte antigen (HLA)-matched donors and failed immunosuppressive therapy (IST) is challenging. Recently, umbilical cord blood transplantation (CBT) after non-myeloablative therapy has been reported in adult but not in childhood SAA. However, most cases resulted in mixed donor chimerism and incomplete hematological recovery. We reported an 11-yr-old girl with recurred SAA 5 yr after IST who underwent unrelated donor CBT after a modified regimen. This patient had renal and cardiac dysfunction, and lacked suitable bone marrow donors. The 3.9 x 10(7)/kg CB cells from an HLA one-locus mismatched unrelated donor were infused after conditioning with total body irradiation (5 Gy), melphalan (120 mg/m(2)), and fludarabin (120 mg/m(2)). Hematological recovery was favorable in complete chimerism. A major complication was only skin graft-versus-host disease (grade I). CB could be an alternate stem cell source for childhood SAA after modified preparative regimen.

Asunto(s)

Anemia Aplásica/terapia , Trasplante de Células Madre de Sangre del Cordón Umbilical , Histocompatibilidad , Acondicionamiento Pretrasplante , Niño , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Prueba de Histocompatibilidad , Humanos , Melfalán/administración & dosificación , Agonistas Mieloablativos/administración & dosificación , Prednisolona/administración & dosificación , Índice de Severidad de la Enfermedad , Factores de Tiempo , Quimera por Trasplante , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal Total/métodos

RESUMEN

Bronchial leiomyoma is a rare disease in children. Recently, the association of leiomyoma and HIV infection was reported. We describe a boy with a cellular immunodeficiency, who had endobronchial leiomyoma. The tumor cells were positive for Epstein-Barr virus-encoded RNA-1 (EBER-1) and Epstein-Barr virus-determined nuclear antigen-2, suggesting a role of Epstein-Barr virus in the pathogenesis of leiomyoma.

Asunto(s)

Neoplasias de los Bronquios/virología , Antígenos Nucleares del Virus de Epstein-Barr/análisis , Síndromes de Inmunodeficiencia/complicaciones , Leiomioma/virología , ARN Viral/análisis , Neoplasias de los Bronquios/complicaciones , Neoplasias de los Bronquios/cirugía , Niño , Complemento C2/deficiencia , Complemento C9/deficiencia , Humanos , Leiomioma/complicaciones , Leiomioma/cirugía , Masculino , Infecciones Tumorales por Virus/genética

RESUMEN

We report a case of juvenile xanthogranuloma (JXG) having progressive pancytopenia for 6 months until the proliferating skin lesions. A 2-month-old infant presented recurrent fever, anemia, and hepatosplenomegaly mimicking hemophagocytic lymphohistiocytosis (HLH) or juvenile myelomonocytic leukemia (JMML). At 8 months of age, the biopsy of a growing papule on the elbow made the diagnosis. Bone marrow (BM) specimens showed clustering foamy cells including hemophagocytosis by histiocytes. Treatment with etoposide followed by vinblastine plus prednisolone (PSL) therapy improved the disease. Although JXG is a benign non-Langerhans cell histiocytosis, the multisystem-visceral form should be considered as a potential aggressive disease when associated with BM failure in early infancy.

Asunto(s)

Pancitopenia/etiología , Xantogranuloma Juvenil/complicaciones , Xantogranuloma Juvenil/patología , Trastornos de la Coagulación Sanguínea/etiología , Médula Ósea/patología , Hepatomegalia/etiología , Humanos , Lactante , Masculino , Esplenomegalia/etiología

RESUMEN

An 11-year-old boy with severe chronic active Epstein-Barr virus infection (CAEBV) underwent successful cord blood transplantation (CBT) after consecutive failure of peripheral blood and bone marrow transplantation from his HLA-mismatched mother. CB cells from an unrelated donor were infused after conditioning with total body irradiation (12 Gy), melphalan (120 mg/m(2)), and etoposide (600 mg/m(2)). Complete remission without circulating EBV-DNA has continued for 15 months after a delayed hematologic recovery. This is the first successful report of CBT for CAEBV. CB may therefore be an alternate source of stem cells for the curative treatment of CAEBV, despite the absence of EBV-specific cytotoxic T lymphocytes.

Asunto(s)

Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Infecciones por Virus de Epstein-Barr/terapia , Terapia Recuperativa/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Enfermedad Crónica , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Inducción de Remisión/métodos , Insuficiencia del Tratamiento , Irradiación Corporal Total

Asunto(s)

Proteínas Portadoras/genética , Anomalías Craneofaciales/genética , Mutación , Síndromes Neurocutáneos/genética , Pueblo Asiatico/genética , Anomalías Craneofaciales/complicaciones , Femenino , Humanos , Lactante , Proteína con Dominio Pirina 3 de la Familia NLR , Síndromes Neurocutáneos/complicaciones , Síndromes Neurocutáneos/patología , Piel/patología

RESUMEN

Febrile seizures (FSs) are the commonest form of convulsions. A genetic predisposition to FSs is known, based on family studies, twin studies, and complex segregation analysis. Simple FSs may be more homogenous in their clinical manifestations, and show better agreement with the multifactorial inheritance theory than the complex type. Interleukin-1 (IL-1) beta is one of the pro-inflammatory cytokines that are postulated to be involved in the development of FSs. To determine whether or not function-related polymorphisms of the IL-1beta (IL1B) gene are associated with susceptibility to simple FSs, the genotypes for two biallelic polymorphisms in the promoter region at positions -31 and -511 of the IL1B gene were determined by means of PCR-restriction fragment length polymorphism in 229 FS patients (108 sporadic and 60 familial simple FS, and 61 complex FS patients) and 158 controls. IL1B -31C/T, a TATA box polymorphism, has been found to be in complete linkage disequilibrium with the IL1B -511C/T polymorphism. Sporadic simple FS patients exhibited significantly higher frequencies of IL1B -31C/-511T alleles and homozygotes than controls (uncorrected p = 0.0094 and 0.0029, corrected p = 0.038 and 0.035, respectively), while no differences were observed in patients with all or familial simple FSs versus controls. There were no significant differences in the frequencies of -31C/T and -511C/T in the IL-1beta promoter gene between complex FS patients and controls. The present study suggests that the IL-1beta gene contributes to a genetic susceptibility to the development of simple FSs of sporadic occurrence.

Asunto(s)

Pruebas Genéticas/métodos , Interleucina-1/genética , Polimorfismo Genético , Medición de Riesgo/métodos , Convulsiones Febriles/epidemiología , Convulsiones Febriles/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Niño , Preescolar , Análisis Mutacional de ADN/métodos , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Incidencia , Japón/epidemiología , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Factores de Riesgo , Convulsiones Febriles/genética

RESUMEN

Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare complication of adult systemic lupus erythematosus (SLE). This is the first report of a pediatric patient with BOOP as an initial presentation of SLE. She had dyspnea, cough, arthralgia, and erythema on her face. Laboratory examinations revealed pancytopenia, low serum levels of complements, and positivity for anti-nuclear antibody, anti-double stranded DNA antibody, and anti-SM antibody. Her respiratory symptoms, pulmonary function tests, and radiologic findings showed significant improvement after treatment with oral prednisolone. Although it is a rare complication among the pleuro-pulmonary manifestations in SLE, BOOP can be the first presentation, even in pediatric patients.

Asunto(s)

Neumonía en Organización Criptogénica/etiología , Lupus Eritematoso Sistémico/complicaciones , Adolescente , Neumonía en Organización Criptogénica/diagnóstico , Neumonía en Organización Criptogénica/terapia , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Prednisolona/uso terapéutico , Radiografía , Resultado del Tratamiento

RESUMEN

The best strategy of hematopoietic stem cell (HSC) transplantation for low-birthweight (LBW) infants with severe combined immunodeficiency (SCID) remains to be determined. To avoid the toxicity of drugs used for the transplantation and the risk of graft-versus-host disease (GVHD), the authors performed allogeneic bone marrow HSC transplantation with a combination of CD34 selection and T-cell depletion in a LBW infant with X-linked SCID. The authors analyzed the process of T-cell reconstitution after the transplantation in this patient. The patient was born at 30 weeks and 2 days' gestational age via cesarean section. He was diagnosed as having SCID at birth. The patient received a transplant of 1 million CD34+ cells/kg body weight. Immunologic reconstitution was investigated by means of phenotypic analysis of T cells and genetic analysis of coding joint T-cell receptor rearrangement excision circle expression. Increases in donor-derived NK cells and T cells were observed 2 and 3 months after the transplantation, respectively. The patient had no infectious complications or GVHD despite the presence of SCID and prematurity-associated immunodeficiency. Analysis of T-cell regeneration pathways revealed that T cells reconstituted mainly via the thymus-dependent pathway. T-cell-depleted CD34+ cell transplantation would be a safe and useful therapy for LBW infants with SCID.

Asunto(s)

Purgación de la Médula Ósea , Inmunodeficiencia Combinada Grave/terapia , Trasplante de Células Madre , Antígenos CD34 , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Masculino , Fenotipo , Inmunodeficiencia Combinada Grave/genética , Hermanos , Linfocitos T , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

UNLABELLED: CD3delta deficiency is a recently identified rare form of severe combined immunodeficiency. We analysed the CD3delta gene in a Japanese family with severe combined immunodeficiency. The patients lacked T-cells with normal numbers of B-cells and natural killer cells in peripheral blood. We found a novel homozygous mutation in the splicing acceptor site of intron 2 (IVS2-2A --> G) in these patients. Analysis of patients' mononuclear cells revealed the CD3delta splicing abnormality. Chest X-ray films and computed tomography revealed small sized thymuses in these patients. CONCLUSION: The CD3delta gene should be analysed in patients with severe combined immunodeficiency lacking T-cells with normal B- and natural killer cells irrespective of the thymus size.

Asunto(s)

Empalme Alternativo , Complejo CD3/genética , Intrones , Inmunodeficiencia Combinada Grave/genética , Pueblo Asiatico/genética , Femenino , Humanos , Lactante , Japón , Linfocitos/metabolismo , Masculino , Mutación , Timo/anomalías

RESUMEN

Serum levels of interleukin-16 (IL-16) were measured to investigate its role in the pathophysiology of hemophagocytic lymphohistiocytosis (HLH). Serum IL-16 levels in patients with acute HLH were significantly higher than those in healthy controls and patients with infectious mononucleosis. They returned to normal levels in the convalescent phase of the disease. In contrast to serum interferon-gamma (IFN-gamma) levels, serum IL-16 levels showed a gradual decrease over the course of the disease. Serum IL-16 levels showed a significant positive correlation with serum levels of soluble IL-2 receptor, IFN-gamma, and interleukin-18, body temperature, and serum lactic dehydrogenase (LDH) levels. An increase in IL-16 mRNA expression was detected in the liver of an HLH patient. These results suggest that IL-16 plays an important role in the pathophysiology of HLH by TH1 cell recruitment and activation at organs with inflammation.

Asunto(s)

Biomarcadores/sangre , Histiocitosis de Células no Langerhans/sangre , Mononucleosis Infecciosa/sangre , Interleucina-16/sangre , Temperatura Corporal , Niño , Preescolar , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Histiocitosis de Células no Langerhans/patología , Humanos , Lactante , Mononucleosis Infecciosa/patología , Interferón gamma/sangre , Interleucina-16/genética , Interleucina-18/sangre , L-Lactato Deshidrogenasa/sangre , Hígado/metabolismo , Masculino , Receptores de Interleucina-2/sangre , Células TH1/inmunología , Células TH1/metabolismo

RESUMEN

Chronic active Epstein-Barr virus (EBV) infection is a chronic mononucleosis syndrome associated with clonal proliferation of EBV-carrying T-/natural killer (NK)-cells. High levels of circulating EBV and activated T-cells are sustained during the prolonged disease course, whereas it is not clear how ectopic EBV infection in T-/NK-cells has been established and maintained. To assess the biological role of activated T-cells in chronic active EBV infection (CAEBV), EBV DNA and cellular gene expressions in peripheral T-cells were quantified in CAEBV and infectious mononucleosis (IM) patients. In CAEBV, HLA-DR(+) T-cells had higher viral load and larger amounts of IFN gamma, IL-10, transforming growth factor-beta (TGF beta), and cytotoxic T lymphocyte antigen-4 (CTLA4) mRNA than HLA-DR(-)T-cells. HLA-DR(+) T cells of IM patients transcribed more IFN gamma and IL-10 than their HLA-DR(-)T cells. Expression levels of IFN gamma and forkhead box p3 (Foxp3) in CAEBV HLA-DR(+) T-cells were higher than in IM HLA-DR(+) T-cells. The effective variables to discriminate the positivity of HLA-DR were IL-10, IFN gamma, CTLA4, TGF beta, and IL-2 in the order of statistical weight. EBV load in CAEBV T-cells correlated with the expression levels of only IL-10 and TGF beta. These results suggest that CAEBV T-cells are activated to transcribe IFN gamma, IL-10, and TGF beta excessively, and the latter two genes are expressed preferentially in the EBV-infected subsets. The dominant expression of regulatory cytokines in T-cells may imply a viral evasion mechanism in the disease.

Asunto(s)

Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/inmunología , Interleucina-10/genética , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Preescolar , Enfermedad Crónica , Infecciones por Virus de Epstein-Barr/virología , Femenino , Expresión Génica , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Lactante , Interferón gamma/genética , Activación de Linfocitos , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo

RESUMEN

OBJECTIVE: To address the role of cord blood (CB) CD25+CD4+ T cells, the gene expressions and function of this subset were analyzed. MATERIALS AND METHODS: CD25+CD4+ T cells fractionated from CB of term and preterm infants were subjected to flow cytometry, quantitative polymerase chain reaction analysis for cytokines, costimulatory molecules, and transcription factors, and functional assays. RESULTS: Human preterm CB contained a high proportion of CD25+CD4+ T cells that declined with gestational age to the level of adult peripheral blood (PB). CD25+ or CD25-CD4+ T cells in CB had a higher frequency of CD45RA+ and CD38+ cells than in PB. CB CD25+CD4+ T cells less frequently expressed CD45RO, CD71, and HLA-DR than PB CD25+CD4+ T cells, despite similar expressions on CB and PB CD25-CD4+ T cells. No expression of IL-10, transforming growth factor-beta, interleukin-4, and interferon-gamma mRNA differed between CB CD25+CD4+ and CD25-CD4+ T cells, in contrast to the high interleukin-10 expression in PB CD25+CD4+ T cells. CTLA-4 was more transcribed in CB and PB CD25+CD4+ T cells than in the counterpart CD25-CD4+ T cells. CD28 or ICOS was similarly expressed in CB and PB T cells. CB CD25+CD4+ T cells effectively suppressed the proliferation of CB CD25-CD4+ T cells in a dose-dependent manner. Human CB and PB CD25+CD4+ T cells preferentially transcribed Foxp3, which governs the regulatory function of this subset in mice. CONCLUSIONS: These results suggest that CB contains CD25+CD4+ regulatory T cells as a functionally mature population with naive phenotype. This subset may naturally arise and decline in fetus to play a potential immunoregulatory role in intrauterine life.

Asunto(s)

Linfocitos T CD4-Positivos/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Sangre Fetal/inmunología , Regulación de la Expresión Génica/inmunología , Receptores de Interleucina-2/sangre , Linfocitos T/inmunología , Animales , Secuencia de Bases , Técnicas de Cultivo de Célula , Cartilla de ADN , Citometría de Flujo , Factores de Transcripción Forkhead , Edad Gestacional , Humanos , Inmunofenotipificación , Recién Nacido , Recien Nacido Prematuro/sangre , Recien Nacido Prematuro/inmunología , Ratones , Reacción en Cadena de la Polimerasa , Subgrupos de Linfocitos T/inmunología