RESUMEN
OBJECTIVES: Inflammasomes are multiprotein complexes that sense pathogens and trigger biological mechanisms to control infection. Nucleotide-binding oligomerisation domain-like receptor (NLR) containing a PYRIN domain 1 (NLRP1), NLRP3 and NLRC4 plays a key role in this innate immune system by directly assembling in inflammasomes and regulating inflammation. Mutations in NLRP3 and NLRC4 are linked to hereditary autoinflammatory diseases, whereas polymorphisms in NLRP1 are associated with autoimmune disorders such as vitiligo and rheumatoid arthritis. Whether human NLRP1 mutation is associated with autoinflammation remains to be determined. METHODS: To search for novel genes involved in systemic juvenile idiopathic arthritis, we performed homozygosity mapping and exome sequencing to identify causative genes. Immunoassays were performed with blood samples from patients. RESULTS: We identified a novel disease in three patients from two unrelated families presenting diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Molecular screening revealed a non-synonymous homozygous mutation in NLRP1 (c.2176C>T; p.Arg726Trp) in two cousins born of related parents originating from Algeria and a de novo heterozygous mutation (c.3641C>G, p.Pro1214Arg) in a girl of Dutch origin. The three patients showed elevated systemic levels of caspase-1 and interleukin 18, which suggested involvement of NLRP1 inflammasome. CONCLUSIONS: We demonstrate the responsibility of human NLRP1 in a novel autoinflammatory disorder that we propose to call NAIAD for NLRP1-associated autoinflammation with arthritis and dyskeratosis. This disease could be a novel autoimmuno-inflammatory disease combining autoinflammatory and autoimmune features. Our data, combined with that in the literature, highlight the pleomorphic role of NLRP1 in inflammation and immunity. TRIAL REGISTRATION NUMBER: NCT02067962; Results.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Artritis Juvenil/genética , Enfermedades Autoinmunes/genética , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades de la Piel/genética , Adolescente , Argelia , Artritis Juvenil/complicaciones , Artritis Juvenil/inmunología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/inmunología , Linfocitos B/inmunología , Población Negra , Caspasa 1/inmunología , Niño , Consanguinidad , Femenino , Enfermedades Autoinflamatorias Hereditarias/complicaciones , Enfermedades Autoinflamatorias Hereditarias/inmunología , Homocigoto , Humanos , Interleucina-18/inmunología , Masculino , Mutación , Proteínas NLR , Países Bajos , Células Precursoras de Linfocitos B/inmunología , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/inmunología , Síndrome , Población BlancaRESUMEN
A rising incidence of invasive group A Streptococcus infections (IGASI) has been noted in children in the past three decades. The relative frequency of the infection types showed marked differences to IGASI in adults, and severity of the disease resulted in a mortality rate usually comprising between 3.6% and 8.3%. The emm1-type group A Streptococcus (GAS) subclone displaying a particular pattern of virulence factors was widely disseminated and prevalent in children with IGASI while the emm3-type GAS subclone appeared as a recent emerging genotype. However, the implication of these hypervirulent clones in the increase of IGASI in children is still controversial. Recent advances in our knowledge on pathogenesis of IGASI underlined that deregulation of virulence factor production, individual susceptibility, as well as exuberant cytokine response are important factors that may account for the severity of the disease in children. Future changes in IGASI epidemiology are awaited from current prospects for a safe and effective vaccine against GAS. IGASI are complex infections associating septic, toxic, and immunological disorders. Treatment has to be effective on both the etiologic agent and its toxins, due to the severity of the disease associated to the spread of highly virulent bacterial clones. More generally, emergence of virulent clones responsible for septic and toxic disease is a matter of concern in pediatric infectiology in the absence of vaccination strategy.
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Infecciones Estreptocócicas , Streptococcus pyogenes , Niño , Farmacorresistencia Bacteriana , Salud Global , Humanos , Incidencia , Índice de Severidad de la Enfermedad , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas , Streptococcus pyogenes/genética , Streptococcus pyogenes/inmunología , Streptococcus pyogenes/patogenicidad , VirulenciaRESUMEN
Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.
Asunto(s)
Varicela , Púrpura Fulminante , Varicela/complicaciones , Niño , Preescolar , Diagnóstico Tardío/efectos adversos , Humanos , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Proteína S , Púrpura Fulminante/diagnóstico , Púrpura Fulminante/etiología , Púrpura Fulminante/terapia , Estudios RetrospectivosRESUMEN
Infectious diseases can result in unanticipated post-infectious inflammatory reactions (PIIR). Our aim was to explore PIIR in 3 frequent pediatric bacterial invasive infections in France by a retrospective monocentric study. We included children hospitalized between 2003 and 2012 for Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), or Streptococcus pyogenes invasive infections. The PIIR had to have occurred between 3 and 15 days without fever despite an individually tailored antibiotic therapy. A descriptive analysis was carried out to determine PIIR risk factors. We included 189 patients, of whom 72, 79, and 38 exhibited invasive infections caused by S pyogenes, SP, and NM, respectively. The mean age was 44 months. PIIR were observed in 39 cases, occurring after a median of 8 days (5-12), with a median duration of 3 days (2-6). Fever, arthritis, and pleural effusion were observed in 87%, 28.2%, and 25.6%, respectively. In multivariate analysis, PIIR were associated with pleuropneumonia, hospitalization in an intensive care unit (ICU), and elevated C-reactive protein (CRP). PIIR were observed in 20% of children after SP, NM, or S pyogenes invasives infections. Their occurrence was associated with the initial severity but not the etiological microorganism. Further studies are warranted to confirm these findings.
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Infecciones Bacterianas , Enfermedades Transmisibles , Infecciones Estreptocócicas , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Proteína C-Reactiva , Niño , Preescolar , Enfermedades Transmisibles/tratamiento farmacológico , Fiebre/epidemiología , Humanos , Lactante , Estudios Retrospectivos , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/epidemiología , Streptococcus pneumoniae , Streptococcus pyogenesRESUMEN
Neonatal alloimmune neutropenia (NAN) results from neutrophil destruction by transplacental maternal neutrophil-specific immunoglobulin G (IgG) antibodies directed against the antigen inherited from the father. Treatment is usually based on recombinant human granulocyte colony-stimulating factor (G-CSF) and prevention or treatment of infection. We report the case of neutropenia in a newborn discovered because of fetomaternal infection. The bone marrow biopsy showed normal cellularity. Granulocyte typing, granulocyte cross-matching, and serum assays showed anti-neutrophil antibodies specific for human neutrophil antigen-1c, an antigen rarely involved in this disease. This NAN was refractory to G-CSF but responded to intravenous immunoglobulin (IVIG). IVIG should be considered as a second-line treatment in NAN refractory to G-CSF. Clinical trials, however, are required to define the optimal management of NAN, a rare but probably underestimated life-threatening situation for newborns.
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Infecciones por Escherichia coli/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Neutropenia/tratamiento farmacológico , Neutrófilos/inmunología , Adulto , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Recién Nacido , Isoantígenos/sangre , Masculino , Neutropenia/inmunología , Neutropenia/microbiología , Proteínas RecombinantesRESUMEN
Retroviruses have been linked to a variety of diseases such as neoplastic and immunodeficiency disorders and neurologic and respiratory diseases. Recently, a novel infectious human retrovirus, the xenotropic murine leukemia virus-related virus (XMRV), has been identified in cohorts of patients with either a familial type of prostate cancer or chronic fatigue syndrome. The apparent unrelatedness of these diseases raised the question of the potential involvement of XMRV in other diseases.Here, we investigated the presence of XMRV in a selection of pediatric idiopathic infectious diseases with symptoms that are suggestive of a retroviral infection, as well as in children with respiratory diseases and in adult patients with spondyloarthritis (SpA). Using a XMRV env-nested PCR, we screened 72 DNA samples obtained from 62 children hospitalized in the Montpellier university hospital (France) for hematological, neurological or inflammatory pathologies, 80 DNA samples from nasopharyngeal aspirates from children with respiratory diseases and 19 DNA samples from SpA. None of the samples tested was positive for XMRV or MLV-like env sequences, indicating that XMRV is not involved in these pathologies.
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Gammaretrovirus/aislamiento & purificación , Infecciones por Retroviridae/epidemiología , Infecciones por Retroviridae/virología , Adolescente , Adulto , Niño , Preescolar , Francia/epidemiología , Gammaretrovirus/genética , Enfermedades Hematológicas/virología , Humanos , Lactante , Nasofaringe/virología , Enfermedades del Sistema Nervioso/virología , Reacción en Cadena de la Polimerasa/métodos , Infecciones del Sistema Respiratorio/virología , Espondilitis/virologíaRESUMEN
BACKGROUND: Human bocavirus (HBoV) is a ubiquitous, newly described member of the Parvoviridae family frequently detected in the respiratory tract of children, but only few reports provide data proving the link between HBoV and respiratory tract disease (RTD). OBJECTIVES: To evaluate the incidence of HBoV infection in children with RTD; to analyze the clinical features of HBoV infection; and to clinically compare HBoV, respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) infections. STUDY DESIGN: A prospective 1-year study was conducted in children <5 years of age hospitalized with RTD and in asymptomatic control children. RESULTS: Human bocavirus was detected in 55 (10.8%) of the 507 children tested and in none of the 68 asymptomatic control children (P = 0.01). About 80% of these infections occurred between November and March. Coinfection with another virus was observed in 22 (40%) of the HBoV-positive children. HBoV viral load was significantly higher in samples from children with HBoV monoinfection than in those with coinfection. Subsequent detection of HBoV more than 2 months after the initial detection could be documented in 3 children. Clinical features associated with HBoV infection were similar to those observed with either RSV or HMPV infections, but HBoV infections were less severe than RSV infections. CONCLUSIONS: The difference observed in HBoV prevalence between children with RTD and controls provides support for a role of this virus in RTD. The frequent associations of HBoV with other respiratory viruses might be explained by the persistence of HBoV in the respiratory tract. The significance of HBoV viral load in nasopharyngeal secretions as a marker of pathogenicity merits further investigation.
Asunto(s)
Bocavirus/aislamiento & purificación , Infecciones por Parvoviridae/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Distribución por Edad , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Metapneumovirus/aislamiento & purificación , Nasofaringe/virología , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Infecciones por Parvoviridae/diagnóstico , Infecciones por Parvoviridae/virología , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios Prospectivos , Virus Sincitiales Respiratorios , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/virología , Carga ViralRESUMEN
BACKGROUND: In children, surveys on Staphylococcus aureus have focused on specific infections, situations or strains but no study has so far given an overview on S. aureus isolation without any selection. Here, we describe the overall bacteriological and clinical characteristics of S. aureus isolation in children, with a special focus on isolates harbouring tst, sea, and/or luk-PV genes, respectively, encoding the three clinically relevant toxins: toxic shock syndrome toxin-1, enterotoxin A and Panton-Valentine leukocidin. METHODS: Data associated with S. aureus isolation were reviewed: isolation site, infection status, tst, sea and luk-PV genes, antimicrobial susceptibility pattern, agr typing. RESULTS: Three hundred and seventy-seven isolates retrieved from 328 children during S. aureus infection (55.2%) or colonisation (44.8%) were included. tst, sea and luk-PV genes were amplified in 14.3, 9.5 and 5.8% of the isolates, respectively. These isolates were significantly more frequently retrieved during infection (69.1%) than colonisation but differences were observed according to isolation site. Methicillin-resistance was found in 7.2% of the isolates, 78% of which harboured ≥ 1 of the targeted toxin-encoding genes. CONCLUSIONS: This first comprehensive study of S. aureus in children showed S. aureus to be mainly retrieved during infection and a high rate of colonisation, not limited to the nasopharynx. Predominant infections were skin and soft tissue infections where tst was most frequently detected. luk-PV was most commonly detected during bone and joint infections. Isolates harbouring targeted toxin-encoding genes were significantly associated with infections but a quarter of children were asymptomatic carriers representing a reservoir for dissemination of isolates with virulence potency.
Asunto(s)
Antibacterianos/farmacología , Toxinas Bacterianas/genética , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/aislamiento & purificación , Distribución por Edad , Toxinas Bacterianas/metabolismo , Distribución de Chi-Cuadrado , Niño , Preescolar , Farmacorresistencia Microbiana , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Hospitales Universitarios , Humanos , Incidencia , Lactante , Pacientes Internos/estadística & datos numéricos , Masculino , Pruebas de Sensibilidad Microbiana , Pacientes Ambulatorios/estadística & datos numéricos , Medición de Riesgo , Distribución por Sexo , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Estadísticas no ParamétricasRESUMEN
OBJECTIVES: Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. METHODS: SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. RESULTS: No associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P=0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P<0.05). CONCLUSION: TRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies.
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Artritis Juvenil/genética , Complemento C5/genética , Factor 1 Asociado a Receptor de TNF/genética , Uveítis/genética , Edad de Inicio , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: Human metapneumovirus (hMPV) is a newly recognized pathogen associated with respiratory tract disease (RTD). OBJECTIVES: To evaluate the incidence of hMPV infection in children hospitalized with RTD and to analyze the virologic and clinical features of hMPV infection. STUDY DESIGN: All children younger than 5 years of age hospitalized for RTD were included in this 1-year prospective study. hMPV was detected in nasopharyngeal secretions by reverse transcription polymerase chain reaction. The hMPV F gene amplification products were sequenced, and a phylogenetic tree was constructed. Samples were also tested for other respiratory viruses by both direct immunofluorescence assay and virus culture. RESULTS: hMPV, detected in 50 of 589 (8.5%) children, represented the second leading cause of RTD after respiratory syncytial virus (RSV). Infections with hMPV occurred mainly between December and April. hMPV isolates clustered into the 4 subgroups (A1, A2, B1 and B2) currently recognized; the majority (72%) of hMPV isolates belonged to subgroup A1. Among the 35 children infected with hMPV alone, 23 (65.7%) had bronchiolitis, 5 (14.3%) had pneumonia, 2 (5.7%) had asthma exacerbation and 5 (14.3%) had a limited upper RTD. Fifteen (30%) of the hMPV-infected children were coinfected with RSV. As compared with children infected with hMPV or RSV alone, duration of hospitalization and requirement for supplemental oxygen were increased in the hMPV/RSV-coinfected children. CONCLUSIONS: hMPV is a frequent cause of RTD in young children. hMPV/RSV coinfection is frequent and could be more severe than a single hMPV or RSV infection.
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Hospitalización , Metapneumovirus , Infecciones por Paramyxoviridae/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/fisiopatología , Infecciones por Paramyxoviridae/virología , Filogenia , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/fisiopatología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio/fisiopatología , Infecciones del Sistema Respiratorio/virologíaRESUMEN
Mammalian retroviruses cause a variety of diseases in their hosts, including hematological and immunodeficiency disorders. Both human T-cell leukemia (HTLV) and human immunodeficiency (HIV) viruses originated from several independent zoonotic transmissions, indicating that cross-species transmissions from animal to humans may still occur. Thus, as the risk for retroviral transmissions from animals to humans increase, we investigated whether mammalian retroviruses are involved in selected pediatric idiopathic diseases whose symptoms evoke retroviral infections. Blood samples, sera, and synovial fluids, or bone marrow cells were collected from pediatric patients under 18 years of age with different autoimmune idiopathic diseases. Overall, we screened clinical samples from 110 children using sensitive nested and semi-nested PCR strategies targeting env genes, and a C-type retrovirus reverse transcriptase (RT) activity kit. All clinical samples were free of retroviral signatures, indicating the unlikelihood of an etiological role of the retroviruses we assessed in the pediatric diseases we tested.
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Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/patología , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/virología , Retroviridae/aislamiento & purificación , Adolescente , Niño , Preescolar , Productos del Gen env/genética , Humanos , Lactante , Reacción en Cadena de la Polimerasa , ADN Polimerasa Dirigida por ARN/análisis , Retroviridae/genéticaRESUMEN
IMPORTANCE: The type I interferonopathies comprise a recently recognized group of mendelian diseases characterized by an upregulation of type I interferon signaling. These monogenic phenotypes include classic Aicardi-Goutières syndrome and syndromic forms of systemic lupus erythematosus, including familial chilblain lupus and spondyloenchondrodysplasia. Dermatologic features provide a major diagnostic clue to this disease grouping, as exemplified by the recently described stimulator of interferon genes-associated vasculopathy with onset in infancy (SAVI) caused by gain-of-function mutations in TMEM173. OBSERVATIONS: We describe a male child who, from the age of 2 months, had significant cutaneous disease that manifested as red violaceous plaques of the cheeks, nose, ears, fingers, and toes that progressed to gangrenous necrosis. In addition to his severe cutaneous vasculopathy, he experienced recurrent fevers, interstitial lung disease, and failure to thrive. His clinical syndrome was refractory to multiple immunosuppressive therapies. Evidence of marked upregulation of type I interferon signaling was observed in peripheral blood, and genetic testing identified a de novo germline mutation in TMEM173, confirming a diagnosis of SAVI 7 years after the onset of his disease. CONCLUSIONS AND RELEVANCE: This observational report describes a new case of SAVI, a recently defined monogenic inflammatory phenotype, that exemplifies an emerging group of disorders related to primary upregulation of type I interferon signaling.
Asunto(s)
Granulomatosis con Poliangitis/diagnóstico , Interferón Tipo I/genética , Proteínas de la Membrana/genética , Enfermedades Cutáneas Vasculares/diagnóstico , Humanos , Lactante , Masculino , Mutación , Fenotipo , Enfermedades Cutáneas Vasculares/genética , Enfermedades Cutáneas Vasculares/patología , Regulación hacia ArribaRESUMEN
OBJECTIVE: Evaluation of the contribution of molecular tools to the overall diagnosis of infectious diseases in children. METHODS: Results of 16S rDNA analysis (179 children; 228 specimens), combined to specific amplification of Kingella kingae (126 children; 166 osteoarticular specimens), were retrospectively analyzed for samples with inconclusive cultures. RESULT: The overall positive yield in diagnosis was 12.8% of the patients for 16S rDNA PCR, 40.5% for K. kingae PCR and 45.2% for combined use of both methods. Results were related to clinical and biological data (direct examination, certainty/uncertainty of clinical diagnosis, fever, biological markers, previous antibiotics), and to the number of samples analyzed per patient, allowing the identification of specific situations with significant contribution of PCR methods. CONCLUSION: Molecular techniques constitute valuable tools to improve the bacterial infection diagnosis in children; however, specific indications, dedicated samples, and number of analyzed samples per patient are key points to optimize their contribution.
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Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/microbiología , Técnicas de Diagnóstico Molecular , Adolescente , Antibacterianos/uso terapéutico , Biomarcadores , Niño , Preescolar , Enfermedades Transmisibles/tratamiento farmacológico , Femenino , Humanos , Lactante , Recién Nacido , Kingella kingae/genética , Masculino , Infecciones por Neisseriaceae/diagnóstico , Infecciones por Neisseriaceae/microbiología , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Estudios RetrospectivosAsunto(s)
Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virología , Poliomavirus/clasificación , Poliomavirus/aislamiento & purificación , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , ADN Viral/aislamiento & purificación , Femenino , Francia/epidemiología , Humanos , Lactante , MasculinoAsunto(s)
Artritis Infecciosa/complicaciones , Artritis Infecciosa/diagnóstico , Tortícolis/complicaciones , Tortícolis/diagnóstico por imagen , Antibacterianos , Artritis Infecciosa/tratamiento farmacológico , Articulación Atlantoaxoidea/diagnóstico por imagen , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: Acute infectious mononucleosis (AIM) is generally associated with a large EBV B cell reservoir cells and an intense B-cell polyclonal activation whereas the number of quiescent EBV-infected memory B cells in chronically EBV-infected healthy controls is very low. OBJECTIVES: To evaluate the extent and functionality of ex vivo B-cell polyclonal activation, quantify the EBV DNA integrated in B cells, enumerate the functional EBV DNA reservoir in B cells and circulating B cells spontaneously secreting EBV antigens in AIM. STUDY DESIGN: Circulating B cells and B cells differentiating into plamablasts and plasma cells, early (BZLF1)- and late viral antigen (gp350)-secreting-cells (SCs) were enumerated in six AIM patients and seven healthy EBV carriers. RESULTS: In vitro B-cell polyclonal activation induced 8000-24,000 BZLF1- and 1000-3000gp350-SCs/10(6) B cells, respectively. These data suggest that only 11.1-19.5% of cells expressing BZLF1 synthesized gp350 and so completed the EBV-lytic cycle. Furthermore, circulating spontaneous BZLF1- and gp350-SCs that reflect ongoing viral replication were rare (20-120 and 10-30/10(6) B cells, respectively), and their low numbers contrasted with the high levels of circulating plasma cells (1.1-10.2% of CD19(+) B cells). CONCLUSION: The in vivo terminal-B-cell differentiation into plasma cells could unmask EBV B-cell reservoir to specific cytotoxic T-cell response and combined with a predominant abortive functional-EBV-reservoir, strongly contribute to rapid decay of cellular EBV reservoir in AIM.
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Linfocitos B/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Mononucleosis Infecciosa/inmunología , Activación de Linfocitos/inmunología , Enfermedad Aguda , Antígenos Virales/inmunología , Linfocitos B/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/metabolismo , Humanos , Mononucleosis Infecciosa/diagnóstico , Mononucleosis Infecciosa/patología , Linfocitos T Citotóxicos/inmunología , Transactivadores/análisis , Transactivadores/biosíntesis , Transactivadores/metabolismo , Proteínas Virales/análisis , Proteínas Virales/biosíntesis , Proteínas Virales/metabolismo , alfa-Macroglobulinas/inmunologíaRESUMEN
Human bocavirus (HBoV), a new member of the genus Bocavirus in the family Parvoviridae, has been recently associated with respiratory tract infections. We report the epidemiologic and clinical features observed from a 1-year retrospective study of HBoV infection in young children hospitalized with a respiratory tract infection.