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Calcinosis/etiología , Enfermedades del Tejido Conjuntivo/etiología , Síndrome de Down/complicaciones , Síndrome de Down/genética , Femenino , Mutación de Línea Germinal , Heterocigoto , Humanos , Interferón Tipo I/fisiología , Péptidos y Proteínas de Señalización Intracelular/genética , Persona de Mediana Edad , Transducción de SeñalRESUMEN
The ever-increasing metagenomic data necessitate appropriate cataloguing in a way that facilitates the comparison and better contextualization of the underlying investigations. To this extent, information associated with the sequencing data as well as the original sample and the environment where it was obtained from is crucial. To date, there are not any publicly available repositories able to capture environmental metadata pertaining to hydrocarbon-rich environments. As such, contextualization and comparative analysis among sequencing datasets derived from these environments is to a certain degree hindered or cannot be fully evaluated. The metagenomics data management system for hydrocarbon resources (MetaHCRs) enables the capturing of marker gene and whole metagenome sequencing data as well as over 300 contextual attributes associated with samples, organisms, environments and geological properties, among others. Moreover, MetaHCR implements the Minimum Information about any Sequence-hydrocarbon resource specification from the Genomic Standards Consortium; it integrates a user-friendly web interface and relational database model, and it enables the generation of complex custom search. MetaHCR has been tested with 36 publicly available metagenomic studies, and its modular architecture can be easily customized for other types of environmental and metagenomics studies.
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Bases de Datos Genéticas , Hidrocarburos/análisis , Internet , Metagenoma , Programas Informáticos , Interfaz Usuario-ComputadorRESUMEN
Pneumococcal conjugate vaccine (PCV) is recommended for adults with chronic disease. Extensive limb swelling (ELS) is an acute vigorous local inflammatory reaction following vaccination. Predisposing immune system correlates and the influence of ELS on vaccine responses are not known. Here, we report a case of a 67-year-old woman with a history of multiple pneumonias who had a detailed immunological work-up pre-vaccination because of suspected immunodeficiency. Four days following a first vaccination with PCV13 she developed ELS-mimicking erysipelas. Treatment with 20 mg cortisone completely alleviated symptoms within 2 days. Skin biopsy showed a dense dermal and subdermal infiltration dominated by CD4+ T cells and macrophages. In a multiplexed serotype-specific measurement of the anti-pneumococcal IgG response, the patient showed very broad and strong vaccine responses. Pre-vaccination titers were low for the vaccine serotypes. We did not find in vivo nor in vitro evidence of an excessive T cell response to the diphtheria-derived PCV carrier protein. However, we could demonstrate a high antibody titer to a non-vaccine serotype, indicating in vivo pre-exposure to pneumococcus bacteria. Thus, traces of pneumococcal proteins included in PCV13 may have boosted pre-existing pneumococcus-specific T helper cells, which subsequently orchestrated ELS. Our case raises awareness for the risk of vaccine-induced ELS, especially in patients with a history of recurrent pneumococcal disease and thus partial immunity.
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Arteritis de Células Gigantes , Herpesvirus Humano 3 , Herpes Zóster , Humanos , Factores de Riesgo , Linfocitos TRESUMEN
Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC). This approach will fail to identify VODI patients because the disease is not associated with severe T cell lymphopenia at birth; (2) the SP110 gene contains 17 exons, making it a challenge for Sanger sequencing. The recently developed next-generation sequencing (NGS) platforms that can rapidly determine the sequence of all 17 exons are available in only a few laboratories; (3) there is no standard functional assay to test for the effects of novel mutations in Sp110; and (4) it has been difficult to use flow cytometry to identify patients who lack Sp110 because of the low level of Sp110 protein in peripheral blood lymphocytes. We report here a novel flow cytometric assay that is easily performed in diagnostic laboratories and might thus become a standard assay for the evaluation of patients who may have VODI. In addition, the assay will facilitate investigations directed at understanding the function of Sp110.
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Citometría de Flujo/métodos , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Síndromes de Inmunodeficiencia/diagnóstico , Antígenos de Histocompatibilidad Menor/metabolismo , Proteínas Nucleares/metabolismo , Linfocitos T/metabolismo , Adenoviridae/genética , Línea Celular Tumoral , Niño , Preescolar , Femenino , Enfermedad Veno-Oclusiva Hepática/metabolismo , Humanos , Síndromes de Inmunodeficiencia/metabolismo , Leucocitos Mononucleares/citología , Masculino , Antígenos de Histocompatibilidad Menor/genética , Proteínas Nucleares/genéticaRESUMEN
Objectives: Autoantibodies are useful biomarkers for diagnosing and monitoring treatment in some autoimmune diseases. Antibodies against isoforms of 14-3-3 protein have been proposed as biomarkers for the presence of aortic aneurysm in large-vessel vasculitis (LVV). Here, we aimed to evaluate the diagnostic role and potential immunopathological involvement of anti-14-3-3 antibodies in newly diagnosed LVV patients. Methods: Antibodies against three isoforms of 14-3-3 (γ, É and ζ) were measured in 90 subjects: 48 GCA and 3 Takayasu's arteritis (TA) patients, and 39 controls (non-inflammatory and inflammatory diseases), using a multiplexed bead-based immunoassay and immunoprecipitation studies. The positive cut-off value was defined based on young healthy controls. Anti-14-3-3 IgG antibodies in LVV patients were compared with those in controls in order to assess their diagnostic performance, and the relationship of anti-14-3-3 IgG antibodies to the immunohistopathology of artery explants was assessed. Results: Antibodies against all three 14-3-3 isoforms were detected in LVV patients as well as in age-matched inflammatory and non-inflammatory controls. Among LVV patients, detection of antibodies targeting 14-3-3 É and ζ was associated with more severe disease. Detection of antibodies against 14-3-3 γ was linked to latent Toxoplasma gondii infection, a parasite that secrets a 14-3-3 homologue, suggesting potential cross-reactivity. Conclusion: Detection of antibodies against 14-3-3 proteins at the time of LVV diagnosis is not disease-specific. Their presence at high levels in LVV patients with stroke, aortitis and-in a previous study-aneurysm formation may indicate an association with extensive tissue destruction. The relevance of 14-3-3 antibodies in non-LVV patients needs to be investigated in larger cohorts.
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Proteínas 14-3-3/inmunología , Autoanticuerpos/metabolismo , Arteritis de Células Gigantes/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Aortitis/inmunología , Biomarcadores/metabolismo , Femenino , Arteritis de Células Gigantes/diagnóstico , Humanos , Inmunoglobulina G/metabolismo , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/inmunología , Arteritis de Takayasu/inmunología , Toxoplasma/inmunología , Toxoplasmosis/inmunología , Remodelación Vascular/inmunología , Adulto JovenAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Antígeno CTLA-4/genética , Enterocolitis/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Adulto , Enfermedades Autoinmunes/genética , Enterocolitis/genética , Humanos , Masculino , Mutación MissenseRESUMEN
BACKGROUND: Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans. METHODS: 3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells. RESULTS: MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment. CONCLUSION: The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats.
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Epinefrina/sangre , Células Asesinas Naturales/inmunología , Subgrupos Linfocitarios/inmunología , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Glucocorticoides/metabolismo , Estrés Fisiológico/inmunología , Células Cultivadas , Estudios Cruzados , Método Doble Ciego , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Células Asesinas Naturales/metabolismo , Subgrupos Linfocitarios/metabolismo , Masculino , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Adrenérgicos beta 2/genética , Receptores de Glucocorticoides/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
SUMMARY: We previously developed OrthoInspector, a package incorporating an original algorithm for the detection of orthology and inparalogy relations between different species. We have added new functionalities to the package. While its original algorithm was not modified, performing similar orthology predictions, we facilitated the prediction of very large databases (thousands of proteomes), refurbished its graphical interface, added new visualization tools for comparative genomics/protein family analysis and facilitated its deployment in a network environment. Finally, we have released three online databases of precomputed orthology relationships. AVAILABILITY: Package and databases are freely available at http://lbgi.fr/orthoinspector with all major browsers supported. CONTACT: odile.lecompte@unistra.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Algoritmos , Gráficos por Computador , Bases de Datos Factuales , Proteómica/métodos , Análisis de Secuencia de Proteína/métodos , Programas Informáticos , Humanos , Anotación de Secuencia Molecular , FilogeniaRESUMEN
Prosthesis-patient mismatch (PPM) remains a controversial issue with the most recent stented biological valves. We analyzed the incidence of PPM after implantation of the Carpentier-Edwards Perimount Magna Ease aortic valve (PMEAV) bioprosthesis and assessed the early clinical outcome. Two hundred and seventy consecutive patients who received a PMEAV bioprosthesis between January 2007 and July 2008 were analyzed. Pre-, peri- and postoperative data were assessed and echocardiographic as well as clinical follow-up was performed. Mean age was 72+/-9 years, 168 (62.2%) were males. Fifty-seven patients (21.1%) were below 65 years of age. Absence of PPM, corresponding to an indexed effective orifice area >0.85 cm(2)/m(2), was 99.5%. Observed in-hospital mortality was 2.2% (six patients), with a predicted mortality according to the additive EuroSCORE of 7.6+/-3.1%. At echocardiographic assessment after a mean follow-up period of 150+/-91 days, mean transvalvular gradient was 11.8+/-4.8 mmHg (all valve sizes). No paravalvular leakage was seen. Nine patients died during follow-up. The Carpentier-Edwards PMEAV bioprosthesis shows excellent hemodynamic performance. This valve can be implanted in all sizes with an incidence of severe PPM below 0.5%.