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Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy. As most affected infants appear healthy at birth, newborn screening (NBS) is essential to identify and treat patients before the onset of symptoms. Here, we report 47 Brazilian patients investigated between 2009 and 2020 for SCID due to either a positive family history and/or clinical impression and low TRECs. Based on clinical presentation, laboratory finding, and genetic information, 24 patients were diagnosed as typical SCID, 14 as leaky SCID, and 6 as Omenn syndrome; 2 patients had non-SCID IEI, and 1 remained undefined. Disease onset median age was 2 months, but at the time of diagnosis and treatment, median ages were 6.5 and 11.5 months, respectively, revealing considerable delay which affected negatively treatment success. While overall survival was 51.1%, only 66.7% (30/45) lived long enough to undergo hematopoietic stem-cell transplantation, which was successful in 70% of cases. Forty-three of 47 (91.5%) patients underwent genetic testing, with a 65.1% success rate. Even though our patients did not come from the NBS programs, the diagnosis of SCID improved in Brazil during the pilot programs, likely due to improved medical education. However, we estimate that at least 80% of SCID cases are still missed. NBS-SCID started to be universally implemented in the city of São Paulo in May 2021, and it is our hope that other cities will follow, leading to early diagnosis and higher survival of SCID patients in Brazil.

Objectives To rescue medical genetics concepts that are necessary to understand the advances in the genetic-molecular characterization of primary immunodeficiencies, to help in the understanding and adequate interpretation of their results. Source of data Non-systematic literature review, searching for articles since 2000 on PubMed using the terms “genetic evaluation” OR “whole exome sequence” or “whole genome sequence” OR “next generation sequence” AND “immunologic deficiency syndromes” OR “Immune deficiency disease” OR “immune deficiency” NOT HIV. Summary of the data Knowledge of medical genetics is essential for the understanding of the principles of heredity and disease inheritance patterns, types of genetic variants, types of genetic sequencing and interpretation of their results. The clinical and immunophenotypic evaluation of each patient is essential for the correlation with the genetic variants observed in the genetic study of patients with primary immunodeficiencies. The discussion of the benefits and limitations of genetic tests should always guide the performance of genetic tests. Conclusions There are many evident benefits of genetic analysis, such as the definitive diagnosis of the disease, family genetic counseling, and the possibility of a more adequate and accurate management. Cost, access and interpretation of genetic test results are limitations that need continuous improvement. The understanding of the benefits and limits of the several genetic assessment methodologies related to primary immunodeficiencies is essential to obtain more effective results from the sequencing.

Objective: To assess the frequency of baked egg tolerance in IgE-mediated egg allergy patients through the oral food challenge and to assess the tolerance predictability of different skin prick tests, as well as specific serum IgE measurement to egg proteins. Methods: In this cross-sectional study, 42 patients with a diagnosis of egg allergy were submitted to different skin prick tests with egg (in natura, boiled, muffin, ovalbumin, and ovomucoid), and specific IgE to egg white, ovalbumin, and ovomucoid; as well as to the oral food challenge with food containing egg, extensively baked in a wheat matrix. Results: Of the total, 66.6% of patients tolerated the ingestion of egg-containing foods in the oral food challenge. A comparative analysis with positive and negative oral food challenge found no significant differences regarding age, gender, other food allergies, or even specific skin prick tests and IgE values between the groups. Conclusions: The study demonstrated an elevated frequency of baked egg food-tolerant individuals among egg allergy patients. None of the tested markers, skin prick tests, or specific IgE, were shown to be good predictors for identifying baked egg-tolerant patients. The oral food challenge with egg baked in a matrix is central to demonstrate tolerance and the early introduction of baked foods, improving patients’ and families’ quality of life and nutrient intake. Resumo: Objetivo: Avaliar a frequência de tolerância a alimentos assados com ovo em pacientes com alergia ao ovo mediada por IgE por meio do teste de provocação oral e verificar a capacidade de predição de tolerância ao ovo por meio de teste cutâneo de leitura imediata (Skin Prick Test ou SPT) e de dosagem sérica de IgE específica para componentes do ovo. Métodos: Estudo transversal, 42 pacientes com diagnóstico de alergia ao ovo foram submetidos a SPT com ovo (in natura, cozido, bolinho, ovoalbumina e ovomucoide), IgE específica para clara de ovo, ovoalbumina e ovomucoide e ao teste de provocação oral com alimento com ovo extensamente assado em matriz de trigo. Resultados: Dos pacientes, 66,6% toleraram a ingestão do alimento com ovo durante o teste de provocação oral. Não encontramos diferenças em relação a idade, gênero, outras alergias alimentares ou mesmo entre os valores dos SPT e IgE específicas na análise comparativa entre os grupos com teste de provocação oral positivo e teste de provocação oral negativo. Conclusões: Foi demonstrada uma elevada frequência de indivíduos tolerantes a ingestão de alimentos assados com ovo entre os pacientes com alergia a ovo mediada por IgE. Nenhum dos marcadores testados, SPT ou IgE específica, demonstrou ser bom preditor para identificar os pacientes tolerantes. Consideramos que os testes de provocação oral com alimentos com ovo assado sejam fundamentais para a introdução desses assados, melhorar a qualidade de vida e a ingestão de nutrientes dos pacientes e famílias.

Objectives: This study aimed to review the literature on the repercussions of the different inborn errors of immunity on growth, drawing attention to the diagnosis of this group of diseases in patients with growth disorders, as well as to enable the identification of the different causes of growth disorders in patients with inborn errors of immunity, which can help in their treatment. Data sources: Non-systematic review of the literature, searching articles since 2000 in PubMed with the terms “growth”, “growth disorders”, “failure to thrive”, or “short stature” AND “immunologic deficiency syndromes”, “immune deficiency disease”, or “immune deficiency” NOT HIV. The Online Mendelian Inheritance in Man (OMIN) database was searched for immunodeficiencies and short stature or failure to thrive. Data summary: Inborn errors of immunity can affect growth in different ways, and some of them can change growth through multiple simultaneous mechanisms: genetic syndromes; disorders of the osteoarticular system; disorders of the endocrine system; reduction in caloric intake; catabolic processes; loss of nutrients; and inflammatory and/or infectious conditions. Conclusions: The type of inborn errors of immunity allows anticipating what type of growth disorder can be expected. The type of growth disorder can help in the diagnosis of clinical conditions related to inborn errors of immunity. In many inborn errors of immunity, the causes of poor growth are mixed, involving more than one factor. In many cases, impaired growth can be adjusted with proper inborn errors of immunity treatment or proper approach to the mechanism of growth impairment. Resumo: Objetivos: Revisão da literatura sobre as repercussões dos diferentes erros inatos da imunidade sobre o crescimento, chamar a atenção para o diagnóstico desse grupo de doenças em pacientes que apresentem desordens do crescimento, assim como permitir que se identifiquem as diferentes causas de alterações do crescimento em pacientes com erros inatos da imunidade, o que pode auxiliar em seu manejo. Fonte dos dados: Revisão não sistemática da literatura, com busca de artigos desde 2000 no Pubmed com os termos “growth” ou “growth disorders” ou “failure to thrive” ou “short stature” AND “immunologic deficiency syndromes” ou “immune deficiency disease” ou “imune deficiency” NOT HIV. E buscas na base OMIN (Online Mendelian Inheritance in Man) por imunodeficiências e baixa estatura ou falha no crescimento (“failure to thrive”). Síntese dos dados: Há diferentes modos pelos quais os erros inatos da imunidade podem afetar o crescimento e alguns deles podem alterar o crescimento por múltiplos mecanismos simultâneos: síndromes genéticas; afecções do aparelho osteoarticular; afecções do sistema endócrino; redução de aporte calórico; processos catabólicos: perda de nutrientes, assim como afecções inflamatórias e/ou infecciosas. Conclusões: O tipo de erros inatos da imunidade permite prever que tipo de alteração no crescimento devemos esperar. O tipo de alteração no crescimento pode auxiliar no diagnóstico de condições clínicas associadas aos erros inatos da imunidade. Em muitos erros inatos da imunidade, as causas do crescimento deficiente são mistas, envolvem mais de um fator. Em muitos casos, o prejuízo do crescimento pode ser corrigido com o adequado tratamento dos erros inatos da imunidade ou adequada abordagem do mecanismo que causa o prejuízo do crescimento. Keywords: Diseases of the immune system, Immune deficiency syndromes, Growth, Growth disorders, Palavras-chave: Doenças do sistema imune, Síndromes de imunodeficiência, Crescimento, Transtornos do crescimento

Objectives To provide an overview of drug treatment, transplantation, and gene therapy for patients with primary immunodeficiencies. Source of data Non-systematic review of the literature in the English language carried out at PubMed. Synthesis of data The treatment of patients with primary immunodeficiencies aims to control their disease, especially the treatment and prevention of infections through antibiotic prophylaxis and/or immunoglobulin replacement therapy. In several diseases, it is possible to use specific medications for the affected pathway with control of the condition, especially in autoimmune or autoinflammatory processes associated with inborn immunity errors. In some diseases, treatment can be curative through hematopoietic stem cell transplantation (HSCT); more recently, gene therapy has opened new horizons through new technologies. Conclusions Immunoglobulin replacement therapy remains the main therapeutic tool. Precision medicine with specific drugs for altered immune pathways is already a reality for several immune defects. Advances in the management of HSCT and gene therapy have expanded the capacity for curative treatments in patients with primary immunodeficiencies.

Introduction: Cow’s milk protein allergy (CMA) is the most common type of food allergy in childhood and exclusion diet is a challenge for patients. Objective: The study aim was to investigate the frequency of tolerance to baked foods containing milk and evaluate immediate skin prick test (SPT) and specific IgEs for different cow’s milk (CM) protein types as predictors of tolerance to baked foods containing milk for CMA patients. Methods: A cross-sectional study was performed. Fifty-four CMA patients were enrolled and oral food challenge (OFC) was performed with baked product, 6 different milk SPTs and specific IgEs to CM, casein, α-lactalbumin, and β-lactoglobulin. Results: Thirty-nine (72.2%) patients tolerated OFC with baked milk cupcake. CM-specific IgE and casein SPT showed statistical difference between positive and negative OFC groups. Probability curves for baked milk tolerance were created for specific CM IgE (Z = 2.542, p < 0.0110) and casein SPT (Z = 2.290, p < 0.0220) using logistic regression. Conclusions: The high percentage of patients able to tolerate baked goods enables an improvement in intake possibilities and quality of life of CMA patients and families. Specific CM IgE and casein SPT demonstrated to be useful predictors in relation to baked milk tolerance.

Background: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue. Methods: The relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice. Findings: IL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression. Interpretation: IL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function. Fund: Sao Paulo Research Foundation grant 2013/07607-8. Keywords: Interleukin-10, Inflammation, Thermogenesis, Mitochondria, Respiration, Obesity

Early detection of Primary Immunodeficiencies Disorders (PIDDs) is of paramount importance for effective treatment and disease management. Many PIDDs would be strong candidates for newborn screening (NBS) if robust screening methods could identify patients from dried blood spots (DBS) during the neonatal period. As majority of congenital PIDDs result in the reduction or absence of specific proteins, direct quantification of these target proteins represents an attractive potential screening tool. Unfortunately, detection is often limited by the extremely low protein concentrations in blood cells and limited blood volume present in DBS. We have recently developed a robust novel method for quantification of low abundance proteins in DBS for PIDDs using peptide immunoaffinity enrichment coupled to selected reaction monitoring (immuno-SRM). Here, we further generated a multiplexed Immuno-SRM panel for simultaneous screening of eight signature peptides representing five PIDD-specific and two cell-type specific proteins from DBS. In samples from 28 PIDD patients including two carriers, representing X-Linked Agammaglobulinemia (XLA), Wiskott-Aldrich Syndrome (WAS), X-Linked Chronic Granulomatous Disease (XL-CGD), DOCK8 Deficiency and ADA deficiency, peptides representing each disease are significantly reduced relative to normal controls and patient identification had excellent agreement with clinical and molecular diagnosis. Also included in the multiplex panel are cell specific markers for platelets (CD42) and Natural Killer Cells (CD56). In patients with WAS, CD42 levels were found to be significantly reduced consistent with characteristic thrombocytopenia. A patient with WAS analyzed before and after bone marrow transplant showed normalized WAS protein and platelet CD42 after treatment highlighting the ability of immuno-SRM to monitor the effects of PIDD treatment. The assay was readily reproduced in two separate laboratories with similar analytical performance and complete agreement in patient diagnosis demonstrating the effective standardized methods. A high-throughput Immuno-SRM method screens PIDD-specific peptides in a 2.5-min runtime meeting high volume NBS workflow requirements was also demonstrated in this report. This high-throughput method returned identical results to the standard Immuno-SRM PIDD panel. Immuno-SRM peptide analysis represents a robust potential clinical diagnostic for identifying and studying PIDD patients from easily collected and shipped DBS and supports a significant potential for early PIDD diagnosis through newborn screening.

Background The food atopy patch (APT) test has been used in previous studies to help the diagnosis of non-IgE mediated food allergies (FA). The aim of this study was to evaluate the efficacy of different cow's milk APT preparations to predict oral tolerance in children with previous non-IgE-mediated cow's milk allergy (CMA) diagnosis. Methods Thirty-two patients non-IgE-mediated CMA diagnosed by oral food challenge (OFC) were enrolled to perform APT with three different cow's milk preparations (fresh, 2% in saline solution, 2% in petrolatum) and comparing with a new OFC after at least three months of diet exclusion. Results Only six (18.7%) subjects presented positive OFC to cow's milk. No differences in gender, onset symptoms age, OFC age, Z-score, and exclusion period were found between positive and negative OFC patients. Preparations using fresh milk and powdered milk in petrolatum presented sensitivity equal to zero and specificity 92.3% and 96.1%. The preparation using powdered milk in saline solution showed sensitivity and specificity of 33.3% and 96.1%. Two patients presented typical IgE symptoms after OFC. Conclusion Cow's milk APT presented a low efficacy to predict tolerance in patients with previous non-IgE-mediated CMA and should not be used in clinical routine. The presence of typical IgE reactions after OFC hallmark the necessity of previous IgE-mediated investigation for this patient group.

Background: Primary immunodeficiencies (PID) are a heterogeneous group of diseases that cause alterations in the immune system, leading to the increased susceptibility to infections, autoimmune diseases, and malignancies. The aim was to evaluate the presence of clinical manifestations and diagnoses of asthma, rhinitis, and atopic dermatitis in patients diagnosed with PID, and correlate these with allergen sensitization verified by skin prick testing (SPT). Material and Methods: This cross-sectional, descriptive, and observational study was conducted from February 2015 to February 2016. We performed a medical report analysis and SPT for aeroallergens in patients with a PID diagnosis. Results: Thirty-one patients with a PID diagnosis were included. The mean age of the participants was 15.41 years. From the 31 patients, 28 had symptoms suggestive of allergic disease (asthma, rhinitis, and atopic dermatitis) and only 7 presented positive SPT for at least 1 aeroallergen. Conclusion: The frequency of allergenic sensitization in the group of patients with PID and symptoms suggestive of asthma, rhinitis, or atopic dermatitis is lower than that found in the general population, probably due the impairment of IgE formation secondary to their immunologic alterations.

diagnosis of primary immunodeficiency diseases (PID) is still a challenge in many countries in Latin America (LA), especially those that face social and economic problems. The creation of a society was fundamental to combine efforts that resulted in an effective educational program, establishment of a registry and a network to improve diagnosis. Areas covered: The focus of this article is to portray the scenario of PID in LA covering different aspects from different countries. For this, a questionnaire was sent to countries that participate in the Latin American Society for Immunodeficiencies (LASID) registry, with questions related to PID challenges in LA. We realized that today the greatest challenge is the availability of laboratory tests to investigate newly described PIDs. Expert commentary: Despite being faced with many difficulties, the Latin America Society for Immunodeficiencies is supporting clinical immunologists throughout the continent, which has resulted in a greater awareness of these diseases and an increase in the number of diagnosis.

Almost 70 years after establishing the concept of primary immunodeficiency disorders (PIDs), more than 320 monogenic inborn errors of immunity have been identified thanks to the remarkable contribution of high-throughput genetic screening in the last decade. Approximately 40 of these PIDs present with autoimmune or auto-inflammatory symptoms as the primary clinical manifestation instead of infections. These PIDs are now recognized as diseases of immune dysregulation. Loss-of function mutations in genes such as FOXP3, CD25, LRBA, IL-10, IL10RA, and IL10RB, as well as heterozygous gain-of-function mutations in JAK1 and STAT3 have been reported as causative of these disorders. Identifying these syndromes has considerably contributed to expanding our knowledge on the mechanisms of immune regulation and tolerance. Although whole exome and whole genome sequencing have been extremely useful in identifying novel causative genes underlying new phenotypes, these approaches are time-consuming and expensive. Patients with monogenic syndromes associated with autoimmunity require faster diagnostic tools to delineate therapeutic strategies and avoid organ damage. Since these PIDs present with severe life-threatening phenotypes, the need for a precise diagnosis in order to initiate appropriate patient management is necessary. More traditional approaches such as flow cytometry are therefore a valid option. Here, we review the application of flow cytometry and discuss the relevance of this powerful technique in diagnosing patients with PIDs presenting with immune dysregulation. In addition, flow cytometry represents a fast, robust, and sensitive approach that efficiently uncovers new immunopathological mechanisms underlying monogenic PIDs.

Background: Food allergy (FA) prevalence has increased in the last decades, but epidemiologic studies could show overestimated results. The objective of this study is to estimate the prevalence of immediate FA in adults in a region of Central Brazil, using a questionnaire to try to reduce misperceptions about FA reaction. Methods: A cross-sectional study was conducted, enrolling an adult population aged 18-65 years comprised of families in a Central Brazilian city. In the first phase, participants answered a self-administered questionnaire for FA screening. In the second phase, the participants who reported an FA in the first questionnaire were visited to complete the second questionnaire applied by trained researchers. Results: Of the 4,916 adults visited, 1,583 returned a completed questionnaire. Reported FA occurred in 171 (10.8%) subjects, and the more frequent citations were cow's milk, pork, fruits, shrimp, and vegetables. One hundred and four of these individuals completed the second questionnaire, and 15 (1.0%) were considered to have an FA diagnosis. The main foods were fruits, followed by cow's milk, shrimp, pork, and vegetables. Conclusion: After use of a specific questionnaire to recognize possible IgE-mediated FAs, a low frequency of FA was considered in this population. Use of a directed questionnaire administered by trained researchers could be an alternative for epidemiological IgE-mediated FA studies to achieve more accurate results.

Here we report a retrospective cross-sectional study on Esophageal eosinophilia (EsEo) frequency in Brazil, for 2, 425 pediatric patients with symptoms associated with gastroesophageal diseases in 2012. EsEo is defined by ≥15 eosinophils per high power field (400x) and confirmed through histological analyses of esophageal biopsies. Overall, 126 patients had EsEo equating to a frequency of 5.2%. There was a significant difference between the endoscopic features of patients with EsEo, where 10.7% had erosive esophagitis, 3.0% had non-erosive esophagitis and 1% showed normal esophageal mucosa. According to the interaction of the variables in the Classification and Regression Tree Analysis, most patients diagnosed with EsEo were older males with erosive esophagitis. On the other hand, the lowest frequency of EsEo was found among younger females with non-erosive esophagitis/normal mucosa. Environmental conditions, including climate variation and changes, were observed in association with EsEo, supporting a potential role for environmental factors in its pathogenesis. There was an inverse correlation between the number of EsEo, rainfall and humidity. EsEo is a relatively frequent finding in the pediatric population of Brazil with symptoms of gastroesophageal diseases. Both clinical and histological examinations of patients are important for a reliable diagnostic of EsEo cases and to patient care.

Background Epidemiological studies around the world suggest that infection with Toxocara spp. can contribute to the development or worsening of atopic diseases, especially in children. This study investigated the seroprevalence of toxocariasis in atopic children treated at the pediatric clinic of the Federal University of Uberlândia Clinical Hospital, identifying possible relationships with risk factors. Methods The study was conducted between November 2011 and March 2013. Blood samples were collected from 173 children aged 6 to 15 years, who were first subjected to clinical exams and then to a skin-prick test to determine the presence or absence of atopy. Risk factors for toxocariasis were analyzed based on a questionnaire. Serum samples were tested for the presence of IgG antibodies to Toxocara spp. by means of enzyme-linked immunosorbent assay. Results The seroprevalence of Toxocara spp. was 19.6% (24/122) in atopic children and 15% (8/51) in non-atopic children, with no statistical difference. No significant association was found between infection and possible risk factors in atopic and non-atopic children. Conclusions Although no statistical association was found between human toxocariasis and atopy, this study revealed a high seroprevalence of Toxocara spp. in children that may indicate environmental contamination with the parasite's eggs in the area where these children live.

Almost all babies suffering from congenital toxoplasmosis, if undiagnosed and untreated, will develop visual or neurological impairments by adulthood. The aim of this study was to investigate the occurrence of congenital toxoplasmosis in two hospitals from Uberlândia, Brazil. A total of 805 serum samples of cord blood were collected, 500 from public hospital and 305 from private hospital, and all patients answered a questionnaire about pregnancy and newborns. ELISA was accomplished to detect IgG antibodies to Toxoplasma gondii and positive sera were re-tested to verify specific IgM and IgA antibodies in a capture ELISA. Seroprevalence of IgG antibodies against T. gondii was 51.6 per cent in the hospitals, while the frequency of congenital toxoplasmosis was 0.5 per cent, with specific IgM and/or IgA antibodies. The main clinical alteration was chorioretinitis (an inflammatory process of the retina and uveal tract). The high seroprevalence in this population and expressive rate of congenital disease show the requirement of screening programmes for toxoplasmosis during pregnancy.

Objective: To analyze whether the patients with severe infections, admitted in the Pediatric Intensive Care Unit of the Hospital de Clínicas of the Universidade Federal de Uberlândia, underwent the active screening for primary immunodeficiencies (PID). Methods: Retrospective study that assessed the data records of patients with any severe infections admitted in the Pediatric Intensive Care Unit, covering a period from January 2011 to January 2012, in order to confirm if they performed an initial investigation for PID with blood count and immunoglobulin dosage. Results: In the studied period, 53 children were hospitalized with severe infections in the Pediatric Intensive Care Unit, and only in seven (13.2%) the initial investigation of PID was performed. Among these patients, 3/7 (42.8%) showed quantitative alterations in immunoglobulin G (IgG) levels, 1/7 (14.3%) had the diagnosis of cyclic neutropenia, and 1/7 (14.3%) presented thrombocytopenia and a final diagnosis of Wiskott-Aldrich syndrome. Therefore, the PID diagnosis was confirmed in 5/7 (71.4%) of the patients. Conclusions: The investigation of PID in patients with severe infections has not been routinely performed in the Pediatric Intensive Care Unit. Our findings suggest the necessity of performing PID investigation in this group of patients. Objetivo: Verificar si los pacientes internados en la Unidad de Terapia Intensiva Pediátrica del Hospital de Clínicas de la Universidad Federal de Uberlândia (Brasil) con infecciones graves fueron sometidos a la busca activa de inmunodeficiencias primarias (IDP). Métodos: Estudio transversal retrospectivo realizado en la Unidad de Terapia Intensiva Pediátrica. Se incluyeron pacientes con diagnóstico de cualquier infección grave admitidos de enero de 2011 a enero de 2012. Se verificó si los pacientes admitidos realizaron la investigación inicial para IDP con hemograma y dosis de inmunoglobulinas. Resultados: En el periodo estudiado, 53 niños fueron internados con infecciones graves, siendo que solamente siete (13,2%) realizaron investigación inicial para IDP. De esos pacientes, 3/7 (42,8%) tenían alteraciones cuantitativas de los niveles de inmunoglobulinas G (IgG), 1/7 (14,3%) presentó diagnóstico de neutropenia cíclica y 1/7 (14,3%), plaquetopenia y diagnóstico de síndrome de Wiskott-Aldrich. Por lo tanto, el diagnóstico de IDP se confirmó en 5/7 (71,4%) de los pacientes. Conclusiones: La investigación de IDP en pacientes con infecciones graves no viene siendo realizada de manera rutinera en la Unidad de Terapia Intensiva Pediátrica. Nuestros hallazgos confirman la necesidad de investigar las IDP en ese grupo de pacientes. Objetivo: Verificar se os pacientes internados na Unidade de Terapia Intensiva Pediátrica do Hospital de Clínicas da Universidade Federal de Uberlândia com infecções graves foram submetidos à busca ativa de imunodeficiências primárias (IDP). Métodos: Estudo observacional retrospectivo realizado na Unidade de Terapia Intensiva Pediátrica. Incluíram-se pacientes com diagnóstico de qualquer infecção grave admitidos de janeiro de 2011 a janeiro de 2012. Verificou-se se os pacientes admitidos realizaram a investigação inicial para IDP com hemograma e dosagem de imunoglobulinas. Resultados: No período estudado, 53 crianças foram internadas com infecções graves, sendo que apenas sete (13,2%) realizaram investigação inicial para IDP. Desses pacientes, 3/7 (42,8%) tinham alterações quantitativas dos níveis de imunoglobulina G (IgG), 1/7 (14,3%) apresentou diagnóstico de neutropenia cíclica e 1/7 (14,3%), plaquetopenia e diagnóstico de síndrome de Wiskott-Aldrich. Portanto, o diagnóstico de IDP foi confirmado em 5/7 (71,4%) dos pacientes. Conclusões: A investigação de IDP em pacientes com infecções graves não tem sido realizada rotineiramente na Unidade de Terapia Intensiva Pediátrica. Nossos achados sugerem a necessidade de investigar as IDP nesse grupo de pacientes.

Background To understand the clinical characteristics and the diagnostic procedures in pediatric patients with eosinophilic esophagitis and to evaluate the sensitivity of the patients to food and inhalant allergens. A cross-sectional study was performed in 35 children with eosinophilic esophagitis during the time period from January 2010 to January 2011. The clinical and epidemiological data were obtained using a questionnaire and medical chart analysis. The body mass index for age was used for the nutritional evaluation (via the Z score). The sensitivity to foods and inhalants was evaluated by performing a skin prick test and atopy patch test. Results Patients (35 in total, median age 10 years) with a diagnosis of eosinophilic esophagitis were evaluated. The most prevalent symptoms in the patients were vomiting (71.4%) and abdominal pain (51.4%). Endoscopic alterations were observed in 97.2% of the patients. A good nutritional state was observed in 82.8% of the children. The tests demonstrated the presence of food sensitivities and/or aeroallergens in 27 (77.1%) patients, whereas 8 (22.9%) patients did not test positive in any of the tests performed. Among the patients with positive tests, 24 (68.5%) exhibited sensitivity to aeroallergens and 16 (45.7%) were sensitive to foods. The comparison between the sensitive and insensitive groups displayed statistically significant results with respect to sex, symptom prevalence, and 24-hour esophageal pH monitoring. Conclusions The patients evaluated in this study displayed clinical characteristics of eosinophilic esophagitis similar to those reported in the literature. The sensitivity to foods determined by the tests was less than that observed in prior studies; however, a marked sensitivity to aeroallergens was observed. The different allergen sensitivity profiles observed in this study suggests that, similar to asthma, the eosinophiic esophagitis disease may exhibit several phenotypes.

Background This study was designed to analyze spirometric parameters and cytokine (interferon [IFN] gamma and IL-5) levels in induced sputum from patients with asthma or allergic rhinitis (AR) and nonatopic subjects. Methods Thirty-three subjects aged 18–60 years were enrolled in the present study. Eight patients had asthma without AR symptoms, 16 had AR without asthma symptoms or history, and both groups had positive skin-prick test (SPT) to aeroallergens. The nine remaining subjects were healthy nonatopic subjects with negative SPT to aeroallergens. Spirometry was performed by evaluating the forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV 1 ), and forced expiratory flow between 25 and 75% (FEF 25–75 ) of FVC before and after bronchodilator use. Induced sputum samples were also collected for measuring cytokine (IFN-gamma and IL-5) levels by enzyme-linked immunosorbent assay. Results Significant pre- and postbronchodilator change was observed only for FEV 1 with higher variation values in asthmatic subjects compared with patients with AR (p < 0.05) and nonatopic subjects (p < 0.01). There was no significant difference in pre- and postbronchodilator spirometric parameters among the three groups, although asthmatic patients showed lower prebronchodilator FEF 25–75 values (p = 0.065). IL-5 levels were higher in induced sputum from patients with asthma and AR compared with nonatopic subjects (p = 0.020 and p = 0.032, respectively), but IFN-gamma levels showed no significant difference between the groups. Conclusion Spirometric measurements were not able to show any occurrence of bronchial constriction in patients with AR, but predominant IL-5 levels in induced sputum from these patients reinforce the role of Th2-type immune response in lower respiratory airways that could contribute to the concept of “one airway, one disease.”

We report a severe case of diarrhea in a 62-year-old female HIV-negative patient from whom Giardia lamblia and Isospora belli were isolated. Because unusual and opportunistic infections should be considered as criteria for further analysis of immunological status, laboratory investigations led to a diagnosis of common variable immunodeficiency (CVID). This is the first reported case of isosporiasis in a patient with CVID and illustrates the importance of being aware of a possible link, particularly in relation to primary immunodeficiency. Trata-se de relato de caso de uma paciente de 62 anos, sexo feminino, HIV negativo apresentando um quadro grave de diarréia, sendo isolados Giardia lamblia e Isospora belli. Infecções incomuns e oportunistas devem ser consideradas como um sinal para alerta para que se analise o sistema imunológico. O diagnóstico de imunodeficiência de comum variável foi realizado após investigação. Este é o primeiro caso relatado de isosporíase em pacientes com imunodeficiência comum variável e mostra a importância de estar alerta tambem em relação a imunodeficiências primárias.

We describe in this paper the phenotype–genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:24:16Z No. of bitstreams: 1 WOS000235369300010.pdf: 231346 bytes, checksum: 5213f2e7aec23c3c699a871a8995b890 (MD5) Made available in DSpace on 2014-02-26T17:24:16Z (GMT). No. of bitstreams: 1 WOS000235369300010.pdf: 231346 bytes, checksum: 5213f2e7aec23c3c699a871a8995b890 (MD5) Previous issue date: 2006-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:30:14Z No. of bitstreams: 1 WOS000235369300010.pdf: 231346 bytes, checksum: 5213f2e7aec23c3c699a871a8995b890 (MD5) Made available in DSpace on 2014-05-20T15:30:14Z (GMT). No. of bitstreams: 1 WOS000235369300010.pdf: 231346 bytes, checksum: 5213f2e7aec23c3c699a871a8995b890 (MD5) Previous issue date: 2006-01-01 Considering that little is known about the epidemiology of Neospora caninum infection in humans, particularly in populations with high Toxoplasma gondii infection rates, the present study aimed to investigate the presence of antibodies to N. caninum in T. gondii-seropositive and -seronegative individuals. A total of 256 serum samples divided into four groups (61 samples from human immunodeficiency virus [HIV]-positive patients, 50 samples from patients with neurological disorders, 91 samples from newborns, and 54 samples from healthy subjects) were assessed for N. caninum and T. gondii serologies by indirect fluorescent-antibody test, enzyme-linked immunosorbent assay, and immunoblotting (IB). Immunoglobulin G antibodies to N. caninum were predominantly detected in HIV-infected patients (38%) and patients with neurological disorders (18%), while newborns and healthy subjects showed lower seropositivity rates (5% and 6%, respectively). Seropositivity to N. caninum was significantly associated with seropositivity to T. gondii in both HIV-infected patients and patients with neurological disorders. Seroreactivity to N. caninum was confirmed by IB, with positive sera predominantly recognizing the 29-kDa antigen of N. caninum. The results of this study indicate the presence of N. caninum infection or exposure in humans, particularly in HIV-infected patients or patients with neurological disorders, who could have opportunistic and concurrent infections with T. gondii. These findings may bring a new concern for the unstable clinical health of HIV-infected patients and the actual role of N. caninum infection in immunocompromised patients. Universidade Federal de Uberlândia (UFU), Immunol Lab, BR-38400902 Uberlandia, MG, Brazil Universidade Federal de Uberlândia (UFU), Parasitol Lab, BR-38400902 Uberlandia, MG, Brazil Universidade Federal de Uberlândia (UFU), Clin Hosp, Sect Infect Dis, BR-38400902 Uberlandia, MG, Brazil UNESP, FCAV, Lab Immunoparasitol, Jaboticabal, SP, Brazil UNESP, FCAV, Lab Immunoparasitol, Jaboticabal, SP, Brazil

To evaluate allergens among patients with allergic respiratory disease attended at the Allergy Clinic of the University Hospital-Federal University of Uberlândia.A retrospective study was performed using medical records. Patients were included if their ISAAC questionnaires were correctly filled out and their skin prick tests were positive to at least one of the allergens from Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), Blomia tropicalis (Blo t), Canis familiaris (Can f), Felis domesticus (Fel d), Blattella germanica (Bla g) and Alternaria alternata.Two-hundred and twelve medical records fulfilled the inclusion criteria. Allergic rhinitis was the main clinical diagnosis (32%), followed by concomitant manifestation of asthma and rhinitis (29.7%), and asthma, rhinitis and atopic dermatitis (9.4%). Asthma alone was found only in 1.9% of patients. The total sensitization observed was 73.5%, of which 61.7%, 59.9%, 54.7%, 45.7%, 38.2%, 33.3%, 9.9% were sensitized to Der p, Der f, Blo t, Bla g, Can f, Fel d and Alternaria, respectively. No significant difference was found between allergic disease types and source of allergen sensitization.The highest sensitization in allergic patients under study was to dust mites, especially Der p and Der f. It is noteworthy that the number of patients sensitized to cockroach extract was uncommonly high when compared to previous studies.

Background The role of mite and pet allergens in the development of allergic diseases has been recognized for many years. Objective To determine mite ( Dermatophagoides pteronyssinus [Der p 1] and Dermatophagoides farinae [Der f 1]), cat ( Felis domesticus [Fel d 1]), and dog ( Canis familiaris [Can f 1]) allergen levels in Brazilian private cars. Methods Mite, cat, and dog allergens were measured in dust samples collected from 60 upholstered seats of private vehicles using enzyme-linked immunosorbent assays. Results Mean levels of Der p 1 (0.24 μg/g of dust; range, 0.0–2.05 μg/g of dust) and Der f 1 (0.29 μg/g of dust; range, 0.06–2.07 μg/g of dust) were extremely low in most dust samples analyzed. In contrast, sensitizing mean levels of Can f 1 (1.51 μg/g of dust; range, 0.14–30.96 μg/g of dust) and Fel d 1 (0.43 μg/g of dust; range, 0.02-5.75 μg/g of dust) were observed in 32 (53%) and 12 (20%) samples, respectively. Mean Can f 1 levels were significantly higher in cars whose owners kept dogs at home (3.27 μg/g of dust) than in those without pets (0.57 μg/g of dust; P = .008). There were no significant differences in allergen levels regarding the age of the vehicle or the number of users and whether the owners transport pets inside the vehicles. Conclusions Private cars constitute an important pet, but not mite, allergen reservoir for continuous contamination of the indoor environment. Pet allergens may be present even in cars whose owners do not have pets. Effective measures to reduce allergen exposure in cars should be taken routinely, especially for pet-allergic patients.

The main purpose of the present study was to examine if there is difference in terms of incidence rates of congenital toxoplasmosis among populations assisted in public and private hospitals from Uberlândia, state of Minas Gerais, Brazil. A total of 805 serum samples from cord blood were collected, being 500 from public hospital and 305 from private hospital, and all patients answered a questionnaire about pregnancy and newborns. An indirect enzyme linked immunosorbent assay (ELISA) was performed to detect IgG antibodies to Toxoplasma gondii and the positive samples were retested to verify the presence of specific IgM and IgA antibodies in a capture ELISA. We found significant differences among data from both hospitals with respect to maternal age, origin city, gestational age, number of visits to physicians during pregnancy, type of delivery, and birth weight. Seroprevalence of IgG antibodies against T. gondii for patients from public and private hospitals was 57.6% and 41.9% respectively, and this difference was statistically significant (P < 0.0001). In addition, the frequency of congenital toxoplasmosis measured by the presence of IgM and/or IgA antibodies toward T. gondii was exclusively located in samples from public hospital (0.8%), and no positive sample was seen in private hospital (0%). Considering that almost all babies suffering from congenital toxoplasmosis, if undiagnosed and untreated, will develop visual or neurological impairments by adulthood, the results presented herein emphasized the importance to accomplish screening programs for toxoplasmosis during pregnancy, particularly in the public hospitals, due to the expressive rate of congenital disease showed in the patients attended at these centers.

Objective: To describe the clinical picture, test results, and clinical evolution of patients with cerebral palsy associated with diagnosis of eosinophilic esophagitis, monitored at tertiary centre. Methods: Cross-sectional, retrospective and descriptive study that evaluated the medical records data of pediatric patients with diagnosis of cerebral palsy and eosinophilic esophagitis in a tertiary center of pediatric gastroenterology between August 2005 and August 2013. Results: Seven out of 131 patients with cerebral palsy had the diagnosis of eosinophilic esophagitis. The mean age at diagnosis of eosinophilic esophagitis was 52.3 months and the mean number of eosinophils in esophagus was 35 per high-power field. Symptoms more frequent were recurrent vomiting and disphagia. Endoscopic alterations found were mucosal thickening, vertical lines, mucosal opacificacion and white plaques. Conclusion: The frequency of eosinophilic esophagitis found was higher than in general pediatric population. The investigation of eosinophilic esophagitis should be done regularly in those patients, once this entity could overlap other gastrointestinal diseases. RESUMO Objetivo: Descrever quadro clínico, resultados dos exames e evolução clínica de pacientes com paralisia cerebral associada ao diagnóstico de esofagite eosinofílica, monitorados em um centro terciário. Métodos: Estudo transversal, retrospectivo e descritivo, que avaliou os prontuários médicos de pacientes pediátricos com diagnóstico de paralisia cerebral e esofagite eosinofílica, atendidos em um centro terciário de gastrenterologia pediátrica, entre agosto de 2005 e agosto de 2013. Resultados: Dos 131 pacientes com paralisia cerebral, 7 tiveram o diagnóstico de esofagite eosinofílica no período estudado. A idade média no momento do diagnóstico de esofagite eosinofílica foi 52,3 meses, e o número médio de eosinófilos no esôfago foi de 35 por campo de grande aumento. Os sintomas mais frequentes associados foram vômitos recorrentes e disfagia. As alterações endoscópicas encontradas foram espessamento da mucosa, linhas verticais, opacificação da mucosa e as placas esbranquiçadas. Conclusão: A frequência de esofagite eosinofílica encontrada foi maior que na população pediátrica em geral. A investigação de esofagite eosinofílica deve ser realizada regularmente nos pacientes com paralisia cerebral, pois pode haver uma sobreposição de sintomas de outras doenças gastrintestinais.

In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do paciente, apresentações disponíveis e forma de obtenção deste recurso terapêutico em nosso meio.