RESUMO
The gastrointestinal tract is heavily populated with innate and adaptive immune cells that have an active role in preservation of mucosal homeostasis and prevention of inflammation. Inflammatory bowel diseases are thought to result from dysregulated immune function that is influenced by genetic background, environmental triggers, and microbiome changes. While most inflammatory bowel disease patients present in adolescent years or adulthood, in a minority of cases, the disease develops early in life, and in some of these young patients, a monogenic disease causing intestinal inflammation can be identified. Many of these conditions result from mutations in immune-mediated genes and can present with or without concomitant recurrent infections. In this review, we will discuss the treatment of patients with selected primary immunodeficiencies and inflammatory bowel diseases. We will focus on five conditions resulting from mutations in IL10/IL10 receptor, NADPH oxidase complex, XIAP, LRBA, and CTLA-4.
Assuntos
Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/terapia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Animais , Antígeno CTLA-4/genética , Gerenciamento Clínico , Suscetibilidade a Doenças , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Interleucina-10/deficiência , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/metabolismo , Mutação , NADPH Oxidases/genética , Receptores de Interleucina-10/deficiênciaRESUMO
Very early onset inflammatory bowel disease (VEO-IBD) is defined as IBD presenting before 6 years of age. When compared with IBD diagnosed in older children, VEO-IBD has some distinct characteristics such as a higher likelihood of an underlying monogenic etiology or primary immune deficiency. In addition, patients with VEO-IBD have a higher incidence of inflammatory bowel disease unclassified (IBD-U) as compared with older-onset IBD. In some populations, VEO-IBD represents the age group with the fastest growing incidence of IBD. There are contradicting reports on whether VEO-IBD is more resistant to conventional medical interventions. There is a strong need for ongoing research in the field of VEO-IBD to provide optimized management of these complex patients. Here, we provide an approach to diagnosis and management of patients with VEO-IBD. These recommendations are based on expert opinion from members of the VEO-IBD Consortium (www.VEOIBD.org). We highlight the importance of monogenic etiologies, underlying immune deficiencies, and provide a comprehensive description of monogenic etiologies identified to date that are responsible for VEO-IBD.
Assuntos
Doenças Inflamatórias Intestinais/diagnóstico , Doenças da Imunodeficiência Primária/complicações , Idade de Início , Pré-Escolar , Predisposição Genética para Doença , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/genética , Fenótipo , Doenças da Imunodeficiência Primária/epidemiologiaRESUMO
Aß(1-40) coated 20 nm gold colloidal nanoparticles exhibit a reversible color change as pH is externally altered between pH 4 and 10. This reversible process may contain important information on the initial reversible step reported for the fibrillogenesis of Aß (a hallmark of Alzheimer's disease). We examined this reversible color change by microscopic investigations. AFM images on graphite surfaces revealed the morphology of Aß aggregates with gold colloids. TEM images clearly demonstrate the correspondence between spectroscopic features and conformational changes of the gold colloid.