RESUMEN
Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Activación de Complemento/efectos de los fármacos , Complemento C5/antagonistas & inhibidores , Inactivadores del Complemento/uso terapéutico , Metabolismo Energético/efectos de los fármacos , Hipoproteinemia/tratamiento farmacológico , Inmunidad Innata/efectos de los fármacos , Enteropatías Perdedoras de Proteínas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Biomarcadores/sangre , Antígenos CD55/deficiencia , Antígenos CD55/genética , Complemento C5/metabolismo , Inactivadores del Complemento/efectos adversos , Inactivadores del Complemento/farmacocinética , Predisposición Genética a la Enfermedad , Humanos , Hipoproteinemia/genética , Hipoproteinemia/inmunología , Hipoproteinemia/metabolismo , Mutación , Fenotipo , Enteropatías Perdedoras de Proteínas/genética , Enteropatías Perdedoras de Proteínas/inmunología , Enteropatías Perdedoras de Proteínas/metabolismo , Resultado del TratamientoRESUMEN
Brain abscesses are uncommon complications of bacterial meningitis or sepsis in neonates and infants. The causative pathogens of brain abscess in newborns are various. Of those, Escherichia coli is rarely seen as a pathogen in brain abscess at this age. Herein we reported brain abscesses in twin infants caused by E. coli sepsis. Interestingly, genetic analysis identified heterozygous Toll-like receptor 4 (TLR4) gene mutation in the twins. Because TLR plays an important role in the natural response to bacterial products and initiates specific immune response against these pathogens, this may explain the development of brain abscess in the present case.
Asunto(s)
Absceso Encefálico/genética , ADN/genética , Enfermedades en Gemelos , Infecciones por Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Mutación , Receptor Toll-Like 4/genética , Absceso Encefálico/metabolismo , Absceso Encefálico/microbiología , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Humanos , Recién Nacido , Masculino , Receptor Toll-Like 4/metabolismoRESUMEN
Introduction: Cow's milk protein allergy (CMPA) is the most commonly encountered food allergy in the world, usually seen in infants under the age of 2 years. This study aims to determine the factors including COVID-19 affecting formula compliance of CMPA patients. Methods: This study is a prospective, observational study based on 10 different Paediatric Allergy-Immunology clinics in Turkey. Patients aged between 6 months and 2 years, who were followed up with IgE-mediated CMPA treatment or newly diagnosed and using breast milk and/or formula were included in the study. The sociodemographic characteristics of the patients, their symptoms, the treatments they received, and the effects of the COVID-19 pandemic on adherence to formula were evaluated with a questionnaire administered to the parents. Results: The compliance rate for formula-based treatment was 30.8% (IQR: 28.3, SD: 21.86). The number of patients with a single and multiple food allergy was 127 (51.6%) and 71 (28.9%), respectively. Breastfeeding duration, daily amount of prescribed formula and addition of sweetener to the formula were found to reduce compliance (p = 0.010, p = 0.003, and p = 0.004, respectively). However, it was determined that the patient's height, weight, age at diagnosis, and age of formula onset did not have a significant effect on compliance. Conclusion: It was found that the duration of breastfeeding, the increase in the daily amount of formula requirement, and the addition of sweeteners had adverse effects on formula compliance. There was no significant correlation between the formula adherence of CMPA patients and the pandemic.