Advances in the diagnosis and treatment of hyper-IgM syndrome in children / 国际儿科学杂志

The hyper immunoglobulin M syndrome(hyper-IgM syndrome, HIGM)is a rare X-linked inherited primary immunodeficiency disease(PID)characterized by defective class switch recombination(CSR)with or without somatic hyper mutation(SHM), resulting in normal or increased levels of serum IgM associated with deficiency of immunoglobulin G(IgG), immunoglobulin A(IgA), and immunoglobulin E(IgE)and antibody dysfunction.Most cases have X-linked recessive inheritance, and a few are autosomal-recessive forms.The clinical manifestations include recurrent infections in early age, tumors and autoimmune diseases.The prognosis is poor, especially for HIGM with X-linked recessive inheritance.And if these patients do not be treated timely after birth, most of them will die early.In order to improve pediatricians′ understanding of the disease, and to timely identify and treat HIGM for an improved prognosis, this paper reviews the pathogenesis, clinical manifestations, diagnosis and treatment of HIGM.

Immunological deficiencies: more frequent than they seem to be

Abstract Objective: A review article was carried out, addressing the clinical and epidemiological characteristics of immune system deficiencies, which are associated with or predispose to recurrent infectious processes, autoimmune diseases, auto inflammatory diseases, or neoplasms, and which are classified as inborn errors of immunity (IEI) and secondary immunodeficiencies (SID). Emphasis was placed on the classification of the main signs and symptoms for each organ and system, which will serve as warning signs, to guide the pediatrician in the investigation of the main IEI. In addition, the main secondary changes in the immune system triggered by infections (with emphasis on COVID-19), drugs, chronic diseases, metabolic and nutritional disorders were identified. Sources of data: This review included articles published in the last five years and that were identified in the MEDLINE platform (PubMed). Summary of findings: The recurrence of infectious processes, associated with the severity of the condition and/or unusual profile of the infectious agent, always related to the age range of symptom onset, are the most important findings for suspected diagnosis. Conclusions: Considering this scenario, immunity disorders should be part of the investigation carried out by the general pediatrician, whether they are the innate errors of immunity (primary immunodeficiencies) or secondary immunodeficiencies, so that the diagnosis is attained as early as possible and therapeutic measures are implemented, reducing the morbidity and mortality of these patients.

Gastrointestinal Manifestations of Primary Immunodeficiency Disorders / 胃肠病学

Primary immunodeficiency disorders (PIDDs) contain more than 300 inborn errors of immunity, among which common variable immunodeficiency (CVID) and chronic granulomatous disease (CGD) are relatively common in clinical practice. CVID is characterized by loss of B cell function and impaired antibody production, while CGD is mainly a congenital disorder with defective neutrophil function. In both diseases, the clinical features include an increased susceptibility to infections and may have symptoms resembling non-infectious inflammatory disorders such as inflammatory bowel disease (IBD). The endoscopic and pathologic findings are non-specific and often mimic IBD, gene analysis is important for differential diagnosis. Treatment is not well defined and is mainly empirical. Infections should be treated with broad-spectrum agents covering both bacterial and fungal pathogens. Corticosteroids or immunosuppressors can be used for PIDDs patients with IBD manifestations.

PROTECTIVE LEVELS OF VARICELLA-ZOSTER ANTIBODY DID NOT EFFECTIVELY PREVENT CHICKENPOX IN AN X-LINKED AGAMMAGLOBULINEMIA PATIENT / Nível sérico adequado de anticorpo contra o vírus da varicela-zoster não foi suficiente para prevenir a infecção em criança com agamaglobulinemia ligada ao X

SUMMARY We describe the case of an eight-year-old boy with X-linked agammaglobulinemia who developed mild varicella despite regular intravenous immunoglobulin (IVIG) therapy. He maintained protective antibody levels against varicella and the previous batches of IVIG that he received had adequate varicella-specific IgG levels. The case illustrates that IVIG may not prevent VZV infection.

RESUMO Relatamos o caso de uma criança com agamaglobulinemia ligada ao X, sexo masculino, oito anos de idade, que desenvolveu quadro de varicela leve, apesar do tratamento regular com imunoglobulina intravenosa (IVIG). O paciente mantinha níveis adequados de imunoglobulina (IgG) contra varicela, assim como, os últimos lotes de IVIG por ele recebido também apresentavam níveis adequados do anticorpo específico. O caso ilustra que o tratamento regular com IVIG não é suficiente para prevenir a infecção pelo vírus da varicela-zoster.

Diagnostic Approach to Primary Immunodeficiency Disorders.

Primary immunodeficiency disorders (PIDs) are a heterogeneous group of inherited disorders that affect different components of the immune system. There are more than 150 different disorders which have been described till date. Despite major advances in the molecular characterization of PIDs over the last 20 years, many patients remain undiagnosed or are diagnosed too late with severe consequences. Recognizing different clinical manifestations of PID is the first most important step. It should be followed by use of appropriate diagnostic tools from a vast number of investigations available. This review will focus on important presenting features of PID and laboratory approach for diagnosis of suspected cases of PID.

Triagem neonatal para imunodeficiência combinada grave / Newborn screening for severe combined immunodeficiency

As imunodeficiências primárias (IDP) são uma área recente e aindapouco conhecida da medicina. Pacientes com IDP apresentam, na maior parte dos casos, infecções graves e recorrentes de início precoce, elevada morbidade e mortalidade, resultando frequentemente em sequelas,elevado custo social e sofrimento dos familiares. Embora na Américado Norte e Europa se estime que sua incidência seja semelhante à dafenilcetonúria e do hipotireoidismo congênito (afecções congênitas quecontam com triagem neonatal), ainda faltam dados quanto à sua real incidência na população brasileira.O projeto em desenvolvimento no Instituto de Ciências Biomédicasda USP e Escola Paulista de Medicina da UNIFESP, visa contribuir para o avanço na implementação de testes de triagem neonatal para asimunodeficiências primárias, mais especificamente, ImunodeficiênciasCombinadas Graves, que constituem um grupo de doenças com diferentesdefeitos genéticos, que evoluem para o óbito precoce se não foremdiagnosticadas e tratadas a tempo e a Síndrome de DiGeorge, que seestima ser a síndrome genética de deleção mais prevalente (1:3.000nascidos vivos).Seguindo esta linha de pensamento, nossa hipótese é que no Brasilexiste um número desconhecido de pacientes com IDP não diagnosticadosou subdiagnosticados que após a implementação de técnicas de detecção molecular por triagem neonatal para a SCID e síndrome de DiGeorge, passarão a ser contabilizados e tratados corretamente, diminuindo portanto,a morbidade e mortalidade.

Primary immunodeficiency disorders (PIDD) are a recently-recognizedand relatively unstudied area of medicine. Patients with PIDD frequentlypresent with the early onset of severe recurrent infections, high morbidityand mortality, frequently resulting in sequelae, high social cost, andfamily burden. While in North America and Europe it is estimated thatits incidence is similar to phenylketonuria and congenital hypothyroidism(congenital disorders that rely on neonatal screening), there is a lack ofdata on its actual incidence in Brazil.The project being developed at Institute of Biomedical Sciences,University of São Paulo and Federal University of São Paulo MedicalSchool, aims to contribute to the implementation of neonatal screeningtests for primary immunodeficiencies. More specifically, severe combinedimmunodeficiencies, a group of diseases with several genetic defects,may progress to early death if not diagnosed and treated early in life;and DiGeorge Syndrome, which is estimated to be the most prevalentgenetic deletion syndrome (1:3,000).Our hypothesis is that, in Brazil there is an unknown number ofpatients with undiagnosed or underdiagnosed disease, which, after theimplementation of detection techniques through newborn screening forSCID and DiGeorge Syndrome, will be accounted for and treated properly,reducing therefore, the morbidity and mortality.