Multisystem inflammatory syndrome in children in western countries: decreasing incidence as the pandemic progresses? An observational multicenter international cross-sectional study

Multisystemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children (MIS-C) has been reported worldwide.1–7 The case definition of MIS-C has been estab- lished by different institutions and organizations such as the US Centers for Disease Control and Prevention (CDC) (May 14, 2020),8 the Royal College of Paediatrics and Child Health in the United Kingdom (RCPCH) (May 1, 2020)9,10 and the World Health Organi- zation (WHO) (May 15, 2020).1Postprint (published version

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

In humans, DOCK8 immunodeficiency syndrome is characterized by severe cutaneous viral infections. Thus, CD8 T cell function may be compromised in the absence of DOCK8. In this study, by analyzing mutant mice and humans, we demonstrate a critical, intrinsic role for DOCK8 in peripheral CD8 T cell survival and function. DOCK8 mutation selectively diminished the abundance of circulating naive CD8 T cells in both species, and in DOCK8-deficient humans, most CD8 T cells displayed an exhausted CD45RA+CCR7? phenotype. Analyses in mice revealed the CD8 T cell abnormalities to be cell autonomous and primarily postthymic. DOCK8 mutant naive CD8 T cells had a shorter lifespan and, upon encounter with antigen on dendritic cells, exhibited poor LFA-1 synaptic polarization and a delay in the first cell division. Although DOCK8 mutant T cells underwent near-normal primary clonal expansion after primary infection with recombinant influenza virus in vivo, they showed greatly reduced memory cell persistence and recall. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

As shown by analysis of mice and humans bearing DOCK8-inactivating mutations, DOCK8 plays a cell-autonomous role in survival of naive CD8 T cells, LFA-1 polarization toward the immune synapse, and CD8 T cell memory and recall responses following viral infection

Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative

Treatment with intravenous gammaglobulin in pediatric patients with primary vasculitis

Nowadays intravenous immunoglobulins have been used in differ- ent vasculitis with various results for each condition, being more recommended for its use in Kawasaki disease and ANCA-associated vasculitis. However, there is still no solid evidence to support its use in the entire group of these diseases. We present a review of the existing literature related to the use of intravenous immunoglobulin for the treatment of primary vasculitis in childhood

Human inmmunoglobulin in primary immunodeficiencies

Human immunoglobulin replacement therapy has become a corner- stone in the treatment of patients with primary immunodeficiencies (PID). Currently indicated as first-line therapy for predominantly antibody deficiencies, severe combined immunodeficiencies, and some well-defined syndromes with immunodeficiencies, it is also indicated as adjunct therapy in many other PID. Although considered a high-cost medication, elegant studies had showed that patients correctly treated with human immunoglobulin replacement therapy result in lower costs derived from their health- attention. Major benefits of immunoglobulin replacement therapy include but are not restricted to: protection against infectious processes, organ damage progression-arrest, immune modulation and quality-of-life improvement. Two modalities of treatment are currently used, intravenous and subcutaneous, each has clear advantages and disadvantages when compared to the other, which are presented in this article. The correct use of human immunoglobulin for the treatment of patients with PID translates in better medical-practices improving survival and quality of life of affected patients

Manifestaciones cardiacas en la etapa aguda de la enfermedad de Kawasaki en un hospital pediátrico de tercer nivel en la Ciudad de México

Resumen: Objetivo: Describir las manifestaciones cardiacas en la etapa aguda de la enfermedad de Kawasaki en pacientes atendidos en un hospital de tercer nivel de la Ciudad de México, México. Métodos: Estudio retrospectivo, descriptivo en pacientes con diagnóstico de enfermedad de Kawasaki de agosto de 1995 a diciembre del 2016 en el Instituto Nacional de Pediatría, México. Se estudio la demografía de los pacientes, características clínicas, tratamiento empleado y desarrollo de complicaciones cardiacas en la etapa aguda de la enfermedad. Resultados: Se estudiaron 508 casos de enfermedad de Kawasaki. La edad media al diagnóstico fue de 37.64 ± 35.56 meses. Predominio de pacientes masculinos del 65.4%, con una relación masculino/femenino de 1.88:1. La mayoría de los casos (79.2%) tuvo una presentación completa. La gammaglobulina intravenosa fue administrada en 92.4% de los casos.Veintiocho pacientes (5.5%) desarrollaron arritmias, se presentaron cambios en el segmento ST en 29 pacientes (5.6%) y 5 pacientes desarrollaron isquemia miocárdica.En el ecocardiograma inicial, 51 pacientes (9.9%) presentaron datos de miocarditis, 72 pacientes (14%) datos de pericarditis y 77 casos tuvieron derrame pericárdico (15%). Se detectaron alteraciones en las arterias coronarias en 169 casos (32.9%). Cuatro pacientes fallecieron en la etapa aguda de la enfermedad por complicaciones cardiacas de la enfermedad de Kawasaki. Conclusiones: En México cada vez existen más casos de enfermedad de Kawasaki con un alto porcentaje de manifestaciones cardiacas al diagnóstico. Se requiere de un mayor conocimiento de la enfermedad en México, para poder establecer cuál es la evolución cardiológica de los pacientes en el país. Abstract: Objectives: To describe the cardiac manifestations in the acute phase of patients with Kawasaki disease treated in a third level Children's hospital in Mexico City, Mexico. Methods: A cross-sectional study was conducted in patients with a diagnosis of Kawasaki disease treated in this hospital from August 1995 to December 2016. Information included patient demographics, clinical features, treatment used, electrocardiographic findings, extra-coronary echocardiographic findings, and the development of coronary artery aneurysms in the acute phase of the disease. Results: The study included 508 cases of Kawasaki disease, with a mean age at diagnosis of 37.64 ± 35.56 months (range from 2 to 200 months). Almost two-thirds (65.4%) of the patients were male, with a male/female ratio of 1.88:1. Complete Kawasaki disease was diagnosed in 79.2% of cases. Almost all cases (92.4%) received intravenous immunoglobulin.Twenty-eight patients (5.5%) developed arrhythmias, ST changes developed in 29 patients (5.6%), and 5 patients presented with ischaemic changes.In the initial echocardiographic evaluation, 51 patients (9.9%) were diagnosed with myocarditis, 72 patients (14.0%) with pericarditis and 77 cases (15.0%) developed pericardial effusion. Coronary artery anomalies were detected in 169 cases (32.9%). 32 cases were diagnosed as giant coronary aneurysms. Four patients died from cardiac complications in the acute phase of the disease. Conclusions: There has been an increase in the diagnosis of Kawasaki disease in Mexico. They presented with more cardiac complications than reported in literature. An increased knowledge of Kawasaki disease is required in Mexico in order to establish the cardiac outcomes of this group of patients. Palabras clave: Enfermedad de Kawasaki, Complicaciones cardiacas, Aneurismas coronarios, México, Keywords: Kawasaki disease, Cardiac complications, Coronary artery aneurysms, Mexic