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2.
N Engl J Med ; 367(3): 214-23, 2012 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-22808956

RESUMEN

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS: A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS: We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding α(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P=6.2×10(-89), P=5.6×10(-12,) and P=2.6×10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P=2.1×10(-8)). CONCLUSIONS: This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.).


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Granulomatosis con Poliangitis/genética , Antígenos HLA-DP/genética , Humanos , Complejo Mayor de Histocompatibilidad/genética , Masculino , Poliangitis Microscópica/genética , Mieloblastina/genética , Factores de Riesgo , alfa 1-Antitripsina/genética
3.
BMJ Health Care Inform ; 30(1)2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37940189

RESUMEN

OBJECTIVES: To overcome the barriers of interoperability by sharing simulated patient data from different electronic health records systems and presenting them in an intuitive timeline of events. METHODS: The 'Patient Story' software comprising database and blockchain, PS Timeline Windows interface, PS Timeline Web interface and network relays on Azure cloud was customised for Epic and Lorenzo electonic patient record (EPR) systems used at different hospitals, using site-specific adapters. RESULTS: Each site could view their own clinical documents and view each other's site specific, fully coded test sets of (Care Connect) medications, conditions and allergies, in an aggregated single view. DISCUSSION: This work has shown that clinical data from different EPR systems can be successfully integrated and visualised on a single timeline, accessible by clinicians and patients. CONCLUSION: The Patient Story system combined the timeline visualisation with successful interoperability across healthcare settings, as well giving patients the ability to directly interact with their timeline.


Asunto(s)
Registros Electrónicos de Salud , Programas Informáticos , Humanos , Atención a la Salud , Instituciones de Salud , Hospitales
4.
Clin Immunol ; 137(2): 281-7, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20797908

RESUMEN

To establish the relevance of targeting disease-associated T cells in anti-RNP-associated glomerulonephritis, mice developing nephritis following immunization with U1-70-kd small nuclear ribonucleoprotein (snRNP) were treated with a single dose of irradiated antigen-selected T cell vaccine. T cell receptor usage in nephritic kidneys revealed oligoclonal use of T Cell Receptor V Beta (TRBV) genes as previously found in spleens and lungs of immunized mice with pulmonary disease. The CDR3 regions from T cell isolates showed sequence homology to those in humans with anti-RNP autoimmunity. Following T cell vaccination, urinalysis returned to normal in 5/7 treated mice (71% response rate) whereas all mock-treated mice continued to have an active urinary sediment (Fisher's Exact p=0.02). An oligoclonal population of T cells homologous to those identified in humans with anti-RNP autoimmunity is implicated in disease pathogenesis, and T cell vaccination is associated with a high rate of clinical improvement in established nephritis.


Asunto(s)
Nefritis Lúpica/terapia , Ribonucleoproteína Nuclear Pequeña U1/inmunología , Linfocitos T/inmunología , Vacunación/métodos , Secuencia de Aminoácidos/genética , Animales , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Proliferación Celular , Regiones Determinantes de Complementariedad/genética , Antígenos HLA-DR/genética , Humanos , Glomérulos Renales/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Nefritis Lúpica/orina , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Ribonucleoproteína Nuclear Pequeña U1/genética , Bazo/citología , Bazo/inmunología , Linfocitos T/patología , Urinálisis
5.
J Healthc Inform Res ; 4(4): 395-410, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35415451

RESUMEN

In this pilot study, we explore the feasibility and accuracy of using a query in a commercial natural language processing engine in a named entity recognition and normalization task to extract a wide spectrum of clinical concepts from free text clinical letters. Editorial guidance developed by two independent clinicians was used to annotate sixty anonymized clinic letters to create the gold standard. Concepts were categorized by semantic type, and labels were applied to indicate contextual attributes such as negation. The natural language processing (NLP) engine was Linguamatics I2E version 5.3.1, equipped with an algorithm for contextualizing words and phrases and an ontology of terms from Intelligent Medical Objects to which those tokens were mapped. Performance of the engine was assessed on a training set of the documents using precision, recall, and the F1 score, with subset analysis for semantic type, accurate negation, exact versus partial conceptual matching, and discontinuous text. The engine underwent tuning, and the final performance was determined for a test set. The test set showed an F1 score of 0.81 and 0.84 using strict and relaxed criteria respectively when appropriate negation was not required and 0.75 and 0.77 when it was. F1 scores were higher when concepts were derived from continuous text only. This pilot study showed that a commercially available NLP engine delivered good overall results for identifying a wide spectrum of structured clinical concepts. Such a system holds promise for extracting concepts from free text to populate problem lists or for data mining projects.

6.
Therapy ; 6(3): 433-442, 2009 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-20161373

RESUMEN

The endosomal Toll-like receptors (TLR3, TLR7 and TLR9) have been implicated in the pathogenesis of autoimmune diseases. Their signaling pathways show remarkable similarities and yet the outcomes following activation of each of these TLRs lead to clinically distinct autoimmune disease phenotypes. This review discusses how differences may arise at a molecular and cellular level to account for this diversity of responses. Understanding the roles of individual TLR pathways and the relationships between them and non-TLR innate immune pathways in the pathogenesis of diseases such as systemic lupus erythematosis highlights potential treatment targets for this spectrum of autoimmune diseases.

8.
Clin Neurol Neurosurg ; 112(4): 341-3, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20056313

RESUMEN

We describe the case of a patient with known Wegener's Granulomatosis who developed a spontaneous intradural haematoma in the thoracic spine against a background of a recent relapse in her vasculitis. Decompression resulted in a rapid recovery of lower limb function. We propose involvement of the spinal meninges in the systemic vasculitis as the cause of haemorrhage.


Asunto(s)
Granulomatosis con Poliangitis/complicaciones , Hematoma Subdural/cirugía , Enfermedades de la Columna Vertebral/cirugía , Descompresión Quirúrgica , Femenino , Hematoma Subdural/complicaciones , Humanos , Laminectomía , Extremidad Inferior , Imagen por Resonancia Magnética , Procedimientos Neuroquirúrgicos , Recuperación de la Función , Recurrencia , Enfermedades de la Columna Vertebral/complicaciones , Columna Vertebral/patología , Columna Vertebral/cirugía , Vasculitis/complicaciones , Vasculitis/patología , Adulto Joven
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