Proposal to Screen for Zinc and Selenium in Patients with IgA Deficiency.

The increase in life expectancy can be a consequence of the world's socioeconomic, sanitary and nutritional conditions. Some studies have demonstrated that individuals with a satisfactory diet variety score present a lower risk of malnutrition and better health status. Zinc and selenium are important micronutrients that play a role in many biochemical and physiological processes of the immune system. Deficient individuals can present both innate and adaptive immunity abnormalities and increased susceptibility to infections. Primary immunodeficiency diseases, also known as inborn errors of immunity, are genetic disorders classically characterized by an increased susceptibility to infection and/or dysregulation of a specific immunologic pathway. IgA deficiency (IgAD) is the most common primary antibody deficiency. This disease is defined as serum IgA levels lower than 7 mg/dL and normal IgG and IgM levels in individuals older than four years. Although many patients are asymptomatic, selected patients suffer from different clinical complications, such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Knowing the nutritional status as well as the risk of zinc and selenium deficiency could be helpful for the management of IgAD patients. OBJECTIVES: to investigate the anthropometric, biochemical, and nutritional profiles and the status of zinc and selenium in patients with IgAD. METHODS: in this descriptive study, we screened 16 IgAD patients for anthropometric and dietary data, biochemical evaluation and determination of plasma and erythrocyte levels of zinc and selenium. RESULTS: dietary intake of zinc and selenium was adequate in 75% and 86% of the patients, respectively. These results were consistent with the plasma levels (adequate levels of zinc in all patients and selenium in 50% of children, 25% of adolescents and 100% of adults). However, erythrocyte levels were low for both micronutrients (deficiency for both in 100% of children, 75% of adolescents and 25% of adults). CONCLUSION: our results highlight the elevated prevalence of erythrocyte zinc and selenium deficiency in patients with IgAD, and the need for investigation of these micronutrients in their follow-up.

Bilateral Dacryoadenitis and Central Nervous System Involvement in a Child With Kimura Disease.

Kimura's disease (KD) is a systemic inflammatory condition characterized by lymphadenopathy and subcutaneous nodules in the head and neck region. The lesions have a distinctive histopathological pattern formed by follicular hyperplasia, eosinophilic infiltrates, fibrosis, and vessel proliferation. The disease may occur at all ages but predominates among young males with autoimmune dysfunctions. Visceral and orbital involvement is uncommon. We report a girl with KD who developed bilateral enlargement of the lacrimal glands and a lesion in the left lateral ventricle of the brain indistinguishable from a central nervous system neoplasia. A biopsy of both the lacrimal gland and the lateral ventricle was consistent with KD.

Apocynin and Nox2 regulate NF-κB by modifying thioredoxin-1 redox-state.

The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for leukocyte anti-microbial activity. However its role in cellular redox homeostasis and, consequently, in modulating intracellular signaling pathways remains unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO) results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation, which causes nuclear accumulation of TRX-1 and enhanced transcription of inflammatory mediators through nuclear-factor-(NF)-κB. The NF-κB overactivation is prevented by TRX-1 oxidation using inhibitors of thioredoxin reductase-1 (TrxR-1). The Nox2/TRX-1/NF-κB intracellular signaling pathway is involved in the pathophysiology of chronic granulomatous disease (CGD) and sepsis. In fact, TrxR-1 inhibition prevents nuclear accumulation of TRX-1 and LPS-stimulated hyperproduction of tumor-necrosis-factor-(TNF)-α by monocytes and neutrophils purified from blood of CGD patients, who have deficient Nox2 activity. TrxR-1 inhibitors, either lanthanum chloride (LaCl3) or auranofin (AUR), also increase survival rates of mice undergoing cecal-ligation-and-puncture-(CLP). Therefore, our results identify a hitherto unrecognized Nox2-mediated intracellular signaling pathway that contributes to hyperinflammation in CGD and in septic patients. Additionally, we suggest that TrxR-1 inhibitors could be potential drugs to treat patients with sepsis, particularly in those with CGD.

Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry.

AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.

Gammaglobulin for primary immunodeficiency: when should it be used? / Gamaglobulina para imunodeficiência primária: quando usar?

Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of thewell-known primary immunodeficiencies requiring gammaglobulin replacement therapy. On the other hand this therapy can be used for some diseases that do not belong to this group, like hyper IgM syndrome, immunodeficiency with thymoma and severe combined immunodeficiency. This therapy is a safe procedure and induces dramatic improvement in the clinical outcome of patients, reducing the risks of death and complications.

Anticorpos são componentes essenciais da resposta imunológica adaptativa e apresentam memória imunológica em longo prazo. Defeitos de anticorpos representam aproximadamente metade das imunodeficiências primárias conhecidas e requerem terapia de reposição de gamaglobulina. Por outro lado, esta modalidade terapêutica pode ser usada para algumas outras doenças que não pertencem a este grupo, como síndrome de hiper IgM, imunodeficiência com timoma e imunodeficiência combinada grave. Este tratamento é um procedimento seguro e acarreta em significativa melhora clínica dos pacientes, reduzindo os riscos de morte e complicações.

First report of the Hyper-IgM syndrome Registry of the Latin American Society for Immunodeficiencies: novel mutations, unique infections, and outcomes.

Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.

Infecções de repetição: o que é importante para o pediatra / Recurrent infections: what is important to pediatricians

OBJETIVO: Apresentar uma revisão atualizada sobre infecções de repetição em crianças, abordando importantes aspectos para o pediatra relacionados a infecções em crianças saudáveis e em crianças com imunodeficiências primárias. FONTES DE DADOS: Artigos relacionados ao tema foram coletados dos bancos de dados Medline e Lilacs no período entre 1980 e 2008, tendo sido selecionados artigos de meta-análise, revisão e estudos clínicos realizados em seres humanos, cuja metodologia e discussão estavam bem estruturadas. Também foram incluídos livros-texto nacionais e internacionais pertinentes ao tema. SÍNTESE DOS DADOS: Infecções de repetição são frequentes na clínica pediátrica. Aproximadamente 50 por cento dessas crianças são saudáveis e 10 por cento podem ser imunodeficientes. A criança saudável apresenta crescimento e desenvolvimento normais e se encontra bem entre os episódios infecciosos. As infecções, na maioria das vezes, não têm curso prolongado ou complicado e ocorrem devido ao aumento da exposição a agentes infecciosos do meio ambiente nos primeiros anos de vida. As imunodeficiências primárias geralmente se manifestam como infecções de repetição por microorganismos específicos ou por germes de baixa virulência. Na maioria das vezes, os quadros infecciosos apresentam evolução prolongada, resposta inadequada à antibioticoterapia e elevados riscos de complicações. CONCLUSÕES: O diagnóstico precoce das imunodeficiências primárias é essencial para que medidas terapêuticas sejam rapidamente instituídas, reduzindo os riscos de ocorrência de óbito e complicações.

OBJECTIVE: To present an up-to-date review about recurrent infections in children, addressing important aspects for pediatricians related to infections in healthy children and in children with primary immunodeficiencies. DATA SOURCE: Articles related to the subject were collected from Medline and Lilacs databases between 1980 and 2008, selecting articles of meta-analysis, review and clinical trials in humans, with well-structured methodology and discussion. National and international textbooks relevant to the subject were also included. DATA SYNTHESIS: Recurrent infections are frequent in pediatric clinics. Approximately 50 percent of these children are healthy and 10 percent may be immunodeficient. The healthy child presents normal growth and development and is well between infections. Most times, infections do not have prolonged or complicated evolution, and they occur due to exposure to infectious agents from the environment during the first years of life. Primary immunodeficiencies usually manifest as recurrent infections by specific microorganisms or by low virulence germs. Most of the times, these infections are prolonged, they present inadequate response to antibiotics and a high risk of complications. CONCLUSIONS: An early diagnosis of primary immunodeficiencies is essential so that therapeutic measures may be taken quickly, reducing risks of death and complications.

Primary immunodeficiency diseases: relevant aspects for pulmonologists.

Primary immunodeficiency diseases comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins and natural killer cells, as well as T and B lymphocytes. The study of these diseases has provided essential insights into the functioning of the immune system. Primary immunodeficiency diseases have been linked to over 120 different genes, abnormalities in which account for approximately 180 different forms of these diseases. Patients with primary immunodeficiency diseases are most often recognized because of their increased susceptibility to infections. However, these patients can also present with a variety of other manifestations, such as autoimmune diseases, inflammatory diseases and cancer. The purpose of this article is to update the main aspects of primary immunodeficiency diseases, especially regarding the clinical manifestations related to the diagnosis, emphasizing the need for the early recognition of warning signs for these diseases.

Imunodeficiências primárias: aspectos relevantes para o pneumologista / Primary immunodeficiency diseases: relevant aspects for pulmonologists

As imunodeficiências primárias são um grupo de doenças geneticamente heterogêneas que afetam diferentes componentes da imunidade inata e adaptativa, como neutrófilos, macrófagos, células dendríticas, proteínas do sistema complemento, células natural killer e linfócitos B e T. O estudo dessas doenças tem fornecido importantes entendimentos sobre o funcionamento do sistema imune. Mais de 120 diferentes genes já foram identificados, cujas anormalidades são responsáveis aproximadamente 180 diferentes formas de imunodeficiências primárias. Pacientes com imunodeficiências primárias são frequentemente reconhecidos pela sua elevada suscetibilidade a infecções; porém, esses pacientes podem apresentar também várias outras manifestações, como doenças autoimunes, doenças inflamatórias e câncer. O propósito deste artigo é atualizar os principais aspectos das imunodeficiências primárias, especialmente em relação às manifestações clínicas relacionadas ao diagnóstico, enfatizando a necessidade do reconhecimento precoce dos sinais de alerta para essas doenças.

Primary immunodeficiency diseases comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins and natural killer cells, as well as T and B lymphocytes. The study of these diseases has provided essential insights into the functioning of the immune system. Primary immunodeficiency diseases have been linked to over 120 different genes, abnormalities in which account for approximately 180 different forms of these diseases. Patients with primary immunodeficiency diseases are most often recognized because of their increased susceptibility to infections. However, these patients can also present with a variety of other manifestations, such as autoimmune diseases, inflammatory diseases and cancer. The purpose of this article is to update the main aspects of primary immunodeficiency diseases, especially regarding the clinical manifestations related to the diagnosis, emphasizing the need for the early recognition of warning signs for these diseases.

Complement levels in Brazilian children during and after meningococcal meningitis

OBJETIVO: Avaliar a atividade funcional das vias clássica e alternativa do sistema complemento e os níveis de C3, C4 e fator B durante o primeiro episódio de infecção meningocócica e durante a convalescença. PACIENTES E MÉTODOS: Dez crianças brasileiras com idades entre 8 meses e 8 anos, admitidas de 1991 a 1993, com diagnóstico clínico-laboratorial de meningite meningocócica, foram estudadas durante infecção aguda (até 7 dias do diagnóstico) e no período de convalescença (entre 1 e 6 meses após). C3, C4 e fator B foram quantificados por nefelometria e a atividade lítica das vias clássica e alternativa foi avaliada por método cinético e expressa como tempo necessário para lisar 50% de uma suspensão de eritrócitos (T1/2, expresso em segundos). Baixos valores de T1/2 das vias clássica e alternativa se correlacionam com elevadas atividades de via clássica e via alternativa, respectivamente. RESULTADOS: Observaram-se diferenças significativas entre a atividade lítica da via alternativa durante a infecção e no período de convalescença (282 e 238 segundos, respectivamente, P= .01). Nenhuma diferença foi detectada nos outros parâmetros analisados. CONCLUSÕES: Na presença de meningite meningocócica a via alternativa é preferencialmente ativada, provavelmente devido à maior capacidade da endotoxina meningocócica para ativar esta via, in vivo.

Aleitamento natural e o sistema imunológico / Breast milk and the immunological sistem

O objetivo desta revisão foi descrever os principais componentes imunológicos presentes no leite materno e seus mecanismos de ação, no tocante à defesa contra agentes infecciosos e na prevenção de doenças alérgicas. A revisão foi baseada em pesquisa no Medline e em livros-texto. Os autores concluem que o aleitamento natural é uma importante fonte de substâncias e células imunologicamente ativas, contribuindo para a prevenção de doenças infecciosas, alérgicas e inflamatórias.

Otite média recorrente na infância / Recurrent otitis media in childhood

Os autores fazem revisäo sobre otite média recorrente, na infância, abordando aspectos clinicoepidemiógicos, seus principais agentes etiológicos, alterações imunológicas envolvidas e enfocam a necessidade de adequada propedêutica diagnóstica, propondo os principais exames complementares necessários