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1.
Immunity ; 29(1): 150-64, 2008 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-18631455

RESUMEN

The analysis of patient blood transcriptional profiles offers a means to investigate the immunological mechanisms relevant to human diseases on a genome-wide scale. In addition, such studies provide a basis for the discovery of clinically relevant biomarker signatures. We designed a strategy for microarray analysis that is based on the identification of transcriptional modules formed by genes coordinately expressed in multiple disease data sets. Mapping changes in gene expression at the module level generated disease-specific transcriptional fingerprints that provide a stable framework for the visualization and functional interpretation of microarray data. These transcriptional modules were used as a basis for the selection of biomarkers and the development of a multivariate transcriptional indicator of disease progression in patients with systemic lupus erythematosus. Thus, this work describes the implementation and application of a methodology designed to support systems-scale analysis of the human immune system in translational research settings.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Genómica/métodos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Adolescente , Niño , Biología Computacional/métodos , Progresión de la Enfermedad , Femenino , Humanos , Masculino
2.
J Exp Med ; 204(9): 2131-44, 2007 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-17724127

RESUMEN

Systemic onset juvenile idiopathic arthritis (SoJIA) represents up to 20% of juvenile idiopathic arthritis. We recently reported that interleukin (IL) 1 is an important mediator of this disease and that IL-1 blockade induces clinical remission. However, lack of specificity of the initial systemic manifestations leads to delays in diagnosis and initiation of therapy. To develop a specific diagnostic test, we analyzed leukocyte gene expression profiles of 44 pediatric SoJIA patients, 94 pediatric patients with acute viral and bacterial infections, 38 pediatric patients with systemic lupus erythematosus (SLE), 6 patients with PAPA syndrome, and 39 healthy children. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children. These genes, however, were also changed in patients with acute infections and SLE. An analysis of significance across all diagnostic groups identified 88 SoJIA-specific genes, 12 of which accurately classified an independent set of SoJIA patients with systemic disease. Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified. Thus, leukocyte transcriptional signatures can be used to distinguish SoJIA from other febrile illnesses and to assess response to therapy. Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.


Asunto(s)
Artritis Juvenil/diagnóstico , Artritis Juvenil/epidemiología , Interleucina-1/antagonistas & inhibidores , Leucocitos Mononucleares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Adolescente , Adulto , Edad de Inicio , Anciano , Artritis Juvenil/genética , Artritis Juvenil/terapia , Estudios de Casos y Controles , Niño , Canales de Cloruro/genética , Enfermedades Transmisibles/genética , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Salud , Humanos , Lactante , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/patología , Persona de Mediana Edad , Transcripción Genética/efectos de los fármacos
3.
Proc Natl Acad Sci U S A ; 105(28): 9727-32, 2008 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-18621685

RESUMEN

Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Here, we report on the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to controls. We found 15% of IgG memory B cell antibodies highly reactive and specific for SLE-associated extractable nuclear antigens (ENA) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germ-line forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52, supporting the idea that somatic mutations contributed to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment.


Asunto(s)
Autoanticuerpos/inmunología , Linfocitos B/inmunología , Memoria Inmunológica , Lupus Eritematoso Sistémico/inmunología , Especificidad de Anticuerpos , Antígenos Nucleares , Autoantígenos/inmunología , Humanos , Inmunoglobulina G , Ribonucleoproteínas/inmunología , Antígeno SS-B
4.
J Pediatr ; 151(6): 707-9, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18035159

RESUMEN

We report on 4 children with infantile-onset lobular panniculitis, high fever, uveitis, and systemic granulomatous inflammation, recruited through the International Registry of Pediatric Granulomatous Arthritis. Neither CARD15 nor CIAS1 mutations were found. Despite immunosuppressive therapy, disease course was progressive. Response to anti-tumor necrosis factor monoclonal antibody in 3 patients is of note.


Asunto(s)
Granuloma/complicaciones , Paniculitis/complicaciones , Uveítis/complicaciones , Artritis/complicaciones , Humanos , Inmunosupresores/uso terapéutico , Lactante , Paniculitis/tratamiento farmacológico , Paniculitis/patología , Síndrome
5.
Pediátr. Panamá ; 48(1): 30-34, abril-Mayo 2019.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1000427

RESUMEN

Presentamos el caso de escolar femenina, que debuta con colecistitis y pancreatitis aguda como manifestación inicial del lupus eritematoso sistémico. Consulta por ebre de origen por determinar e hiporexia. Por la persistencia de la fiebre, pérdida de peso y manifestaciones sistémicas se sospecha de una Enfermedad Autoinmune, con rmando el diagnóstico de LES con ANA y antiDNA positivos


We present the case of a school-aged female, who presents with acute cholecystitis and acute pancreatitis as the initial manifestation of systemic lupus erythematosus. She consults with fever of unknown origin and hyporexia. Due to persistent fever, weight loss and systemic manifestations, Autoimmune Disease is suspected, confirming the diagnosis of SLE with positive ANA and anti-DNA with which the diagnosis of SLE was made

6.
Curr Rheumatol Rep ; 7(6): 421-6, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16303100

RESUMEN

Although the pathogenesis of SLE remains poorly understood, there is consensus that it involves a combination of genetic, hormonal, and environmental factors. New technologies applied to genomic and gene expression studies have revealed novel gene mutations and cytokine alterations in this disease. Recently, advances in monoclonal antibodies and recombinant DNA technology have resulted in the development of new drugs to arrest disease progression and restore physiologic immune responses without major side effects. Clinical trials to test several of these novel therapies are currently underway.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Autoinmunidad/fisiología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Factores de Edad , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/metabolismo , Proteínas Reguladoras de la Apoptosis/inmunología , Proteínas Reguladoras de la Apoptosis/metabolismo , Enfermedades Autoinmunes/diagnóstico , Niño , Preescolar , Terapia Combinada , Progresión de la Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Pronóstico , Medición de Riesgo , Análisis de Supervivencia
7.
Pediatr Dermatol ; 22(3): 262-5, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15916580

RESUMEN

Infliximab, a chimeric antitumor necrosis factor alpha monoclonal antibody (anti-TNF alpha), has been recently shown to have a beneficial effect on pyoderma gangrenosum associated with inflammatory bowel disease. Patients with the syndromic triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne, an autoinflammatory process caused by mutations in the CD2 binding protein-1 (CD2BP1) gene, can have severe pyoderma gangrenosum. We describe a 14-year-old patient with this syndrome who was unresponsive to multiple therapies. A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Piodermia Gangrenosa/tratamiento farmacológico , Acné Vulgar/genética , Adolescente , Artritis/genética , Humanos , Infliximab , Masculino , Piodermia Gangrenosa/genética , Síndrome
8.
Curr Opin Rheumatol ; 16(5): 577-87, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15314498

RESUMEN

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the clinical manifestations of SLE in children. Emerging clues on the pathogenesis of the disease based on recent human studies conducted both in children and adults, will also be summarized. RECENT FINDINGS: Pediatric Rheumatologists caring for children with SLE face many challenges. As the life expectancy of these patients improves, new recognized complications such as accelerated atherosclerosis and hypertension emerge as major causes of morbidity. However, few longitudinal studies describing the long term outcome of these children, including the impact of disease and treatment on their physical and psychological development are available. Few prospective interventional studies have been carried out to assess the efficacy of established and novel treatments in the pediatric population. Recently, basic studies aimed at understanding the immune alterations underlying this disease have been performed in children. These studies indicate an important role for interferon-alpha (IFN-alpha) in the pathogenesis of this disease and reveal an overall striking homogeneity of leukocyte gene expression profiles in children and adults with SLE. The contribution of novel gene polymorphisms to disease susceptibility and the sequential breakdown of tolerance to nuclear antigens that precedes clinical manifestations in patients with SLE are among the recent studies that are helping us understand the complex SLE puzzle. SUMMARY: SLE continues to cause significant morbidity in the pediatric age group. A better recognition of the age-specific manifestations and long-term complications of this disease is required to improve its outcome. Understanding its unique pathogenesis will hopefully lead to the development of better, more targeted and less toxic therapies.


Asunto(s)
Lupus Eritematoso Sistémico , Pediatría/tendencias , Reumatología/tendencias , Adolescente , Niño , Preescolar , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/etiología , Lupus Eritematoso Sistémico/patología
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