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Pneumonia is a kind of inflammatory disease characterized by pathogen infection of lower respiratory track. Lipopolysaccharide (LPS) is the main bioactive component of Gram-negative bacteria responsible for inflammatory response. Recently, coniferyl aldehyde (CA) has been reported to play a crucial role because of its anti-inflammatory activity. However, the effect and mechanisms of CA in ameliorating symptoms of acute pneumonia remain unknown. Evaluating and identifying the value and exploring the mechanisms of CA on LPS-mediated WI-38 apoptosis and inflammation were the aims of this study. Here, CCK-8 cell viability assay was applied on WI-38 after treatment with or without LPS at different doses of CA to verify that CA can increase LPS-induced cell viability. Then, quantitative polymerase chain reaction (qPCR) and enzyme-linked-immunosorbent serologic assays (ELISA) suggested that LPS treatment dramatically decreased the expression level of IL-10 (anti-inflammatory factor) while strikingly increasing the expression levels of IL-1β, IL-6, and TNF-α (tumor necrosis factor-α; proinflammatory factor) whereas CA treatment attenuates LPS-induced inflammation of WI-38. Further, flow cytometry and Western blot assay verified that LPS treatment dramatically promoted apoptosis of WI-38 cells, while administration of CA notably inhibited apoptosis of WI-38 cells. Moreover, the Western blot assay hinted that CA could inactivate LPS-induced JAK2–STAT1 signaling pathway. These findings indicated that CA could alleviate LPS-mediated WI-38 apoptosis and inflammation injury through JAK2–STAT1 pathway in acute pneumonia.

Introduction and objectives: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers antimite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals.Methods: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated.Results: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies.Conclusions: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

Introduction Ataxia-Telangiectasia (A-T) is a multi-system disorder that may be associated with endocrine changes, oxidative stress in addition to inflammation. Studies suggest that selenium is a trace element related to protection against damage caused by oxidative stress. Objective To describe the plasma levels of selenium and erythrocyte glutathione peroxidase activity in A-T patients and to relate them to oxidative stress and lipid status biomarkers. Methods This is a cross-sectional and controlled study evaluating 22 A-T patients (age median, 12.2 years old) matched by gender and age with 18 healthy controls. We evaluated: nutritional status, food intake, plasma selenium levels, erythrocyte glutathione peroxidase activity, lipid status, inflammation and oxidative stress biomarkers. Results Adequate levels of selenium were observed in 24/36 (66.7%) in this evaluated population. There was no statistically significant difference between the groups in selenium levels [47.6 μg/L (43.2–57.0) vs 54.6 (45.2–62.6) μg/dL, p = 0.242]. Nine of A-T patients (41%) had selenium levels below the reference value. The A-T group presented higher levels of LDL-c, non-HDL-c, oxidized LDL, Apo B, Apo-B/Apo-A-I1, LDL-c/HDL-c ratio, malondialdehyde [3.8 µg/L vs 2.8 µg/L, p = 0.029] and lower Apo-A-I1/HDL-c and glutathione peroxidase activity [7300 U/L vs 8686 U/L, p = 0.005]. Selenium levels were influenced, in both groups, independently, by the concentrations of oxidized LDL, malonaldehyde and non-HDL-c. The oxidized LDL (AUC = 0.849) and ALT (AUC = 0.854) were the variables that showed the greatest discriminatory power between groups. Conclusion In conclusion, we observed the presence of selenium below the reference value in nearly 40% and low GPx activity in A-T patients. There was a significant, inverse and independent association between selenium concentrations and oxidative stress biomarkers. Those data reinforce the importance of assessing the nutritional status of selenium in those patients.

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disease caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. The parents do not manifest the disease but are ...

INTRODUCTION Mucopolysaccharidoses (MPSs) are a group of rare diseases caused by an intralysosomal accumulation of glycosaminoglycans, resulting in a multisystemic clinical condition characterized by variable degrees of physical-functional impairment. OBJECTIVE To evaluate the functional capacity (FC) of MPS patients and compare with a healthy control group. METHODS This is a cross-sectional study of 6- to 39-year-old patients followed at a medical reference center and compared with their control peers, matched by age and sex. FC was assessed using the Sit-to-Stand Test (SST) and Incremental Shuttle Walk Test (ISWT). Heart rate (HR) and Borg rating of perceived exertion were measured before and after ISWT. HR recovery (HRR) was defined as the HR at the end of the test minus the HR in the second minute after ISWT. RESULTS Nineteen (19) MPS patients, 69% with type II MPS and mean age 17 ± 11 years were evaluated. Every patient was under enzyme replacement therapy. The time to perform the SST was longer in the MPS group (10.6 ± 2.5 s vs. 6.7 ± 1.2 s; p

Objective Allergic sensitization is one of the key components for the development of allergies. Polysensitization seems to be related to the persistence and severity of allergic diseases. Furthermore, allergic sensitization has a predictive role in the development of allergies. The aim of this study was to characterize the pattern of sensitization of atopic patients treated at different pediatric allergy referral centers in Brazil. Methods A nation-wide transversal multicenter study collected data on patients attended in Brazil. Peripheral blood samples were collected to determine the serum levels of allergen-specific IgE. If allergen-specific IgE was higher than 0.1 kUA/L, the following specific components were quantified. Results A total of 470 individuals were enrolled in the study. Mite sensitization was the most frequent kind in all participants. A high frequency of sensitization to furry animals and grasses featured in the respiratory allergies. Regarding components, there was a predominance of sensitization to Der p 1 and Der p 2. It has been verified that having a food allergy, atopic dermatitis, or multimorbidity are risk factors for the development of more severe allergic disease. Conclusion Studies on the pattern of allergic sensitization to a specific population offer tools for the more effectual prevention, diagnosis, and treatment of allergic diseases. Sensitization to dust mites house was the most prevalent in the evaluated sample. High rates of sensitization to furry animals also stand out. Patients with food allergy, atopic dermatitis, or multimorbidity appear to be at greater risk for developing more severe allergic diseases.

Background: Fabry disease (FD) is a rare X-linked storage disorder resulting from the deficient activity of the lysosomal hydrolase α-galactosidase A (α-Gal A). Here we describe a 23-year-old man with FD possessing a novel mutation in the GLA gene, the evaluation of his family, and the functional characterization of the novel variant. Methods: Two generations of a family were screened for FD by clinical symptoms and low enzymatic activity. This step was followed by DNA sequencing that showed a novel GLA missense mutation. To confirm the pathogenicity potential of the mutation, we employed site-directed polymerase chain reaction mutagenesis. GLA wild-type and mutant plasmids were transfected into mammalian cells; RNA and proteins were extracted for expression and analysis of enzymatic activity. Results: The patient presents the variant p.Asn34Asp in the GLA and had several manifestations of FD since adolescence. The investigation of the deficiency of α-Gal A was initiated due to stage 4 of chronic kidney disease. All family members carrying the novel mutation presented early symptoms, including index case’s mother, who received a renal transplant when she was 35 years old. In silico and in vitro analysis confirmed the pathogenic potential of the mutation p.Asn34Asp showing that the enzyme had only 4% of residual activity due to protein misfolding. The ability of the pharmacological chaperone 1-deoxygalactonojirimycin to recover the mutant was confirmed, producing 37.5% of residual activity. Conclusion: In this work, we present a novel missense mutation in GLA that leads to the production of a catalytically competent α-Gal A, which is degraded before its delivery to the lysosome, promoting severe manifestations of FD, with a very similar disease course in affected men and women.

Background Common variable immunodeficiency (CVID) is an inborn errors of immunity, that leads to recurrent chronic infections and autoimmune/ inflammatory diseases and neoplasms. It is considered that these condition is related to persistent this immune-inflammatory stimulation and increased oxidative stress. A positive impact on the survival of patients with an inborn error of immunity was observed with advanced clinical care protocols, thus raising concerns about the risk of developing other associated chronic diseases, such as atherosclerosis. Studies suggest that selenium (Se) is a protective trace element against damage caused by oxidative stress. Thus, it is postulated that adequate consumption reduces the risk of some chronic diseases. Results Se median levels (ug/L) [45.6 (37.3–56.2) vs. 57.8 (46.0–66.0); p = 0.004] and GPX activity (U/L) [7682 (6548–8446) vs. 9284(8440–10,720); p = 0,002) were significantly lower in patients compared to controls. Inadequacy of Se levels was observed in 50% of the patients. There was a higher percentage of high values of C-reactive protein in the group of CVID patients compared to controls [8 (36.4%) vs. 2 (11.1%); p = 0.082]. Higher concentrations of oxidized LDL (45.3 mg/dL vs. 33.3 mg/dL; p = 0.016) and lower concentrations of Apo A-1 (98.5 mg/dL) vs. 117.0 mg/dL; p = 0.008) were observed in the CVID group compared to the control. There was a significant and positive correlation between Se plasma levels and apolipoprotein A-1 concentrations in CVID group (rho = 0.577; p = 0.001). Se values less than 46 μg / L (OR = 3.590; 95% CI 1.103 to 11.687; p = 0.034) and GPX activity below the 4th quartile (OR = 21.703; 95% CI 2.534 to 185.914; p = 0.005) were independently associated, after adjustment for age, overweight and dyslipidemia, with the CVID group (Table 5). Conclusion This study showed an higher percentage of high us-CRP, lower values of plasma Se and GPX activity, higher concentrations of LDLox and lower levels of Apo A-1 in CVID patients in comparison to controls, suggesting oxidative stress and cardiovascular risk.These data point to the importance of assessing the Se status and cardiovascular risk in these patients.

Purpose: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and to identify factors influencing the outcome of infection.Methods: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. Results: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n=53). The infection presented mostly as asymptomatic (n=21) and mild (n=66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex related susceptibility and observed a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. Conclusion: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. Patients with complement deficiencies had milder COVID-19. However, the type of IEI was not a determining factor for severity. The severity of SARS-CoV-2 infection seems to be more related to older age, higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Background Ataxia telangiectasia is one of the most common causes of autosomal recessive cerebellar ataxias. However, absence of telangiectasia, normal levels of alpha-fetoprotein and negative genetic test may direct to alternative diagnosis with similar phenotypes such as ataxia telangiectasia-like disorders (ATLD). Cases We report two instructive cases of ATLD: the first case with ataxia telangiectasia-like disorder type 1 related to MRE11A gene, and the second case with ataxia telangiectasia-like disorder type 2 related to PCNA gene. Literature review ATLD is an unusual group of autosomal recessive diseases that share some clinical features and pathophysiological mechanisms with ataxia telangiectasia (AT). ATLD may be associated with mutations in the MRE11A (ATLD type 1) and PCNA (ATLD type 2) genes. ATLD belongs to the group of chromosomal instability syndromes. The reason for the term ATLD is related to the similar pathophysiological mechanisms observed in AT, which is characterized by chromosomal instability and radiosensitivity. Conclusions In this review, the main clinical features, biomarkers, brain imaging and genetics of ATLD are discussed. Mutations in the MRE11A and PCNA genes should be included in the differential diagnosis for early onset cerebellar ataxia with absence of telangiectasia and normal levels of alpha-fetoprotein.

Background Primary angioedema (PA) is a complex disorder, presenting multiple hereditary (hereditary angioedema) and acquired subtypes (acquired angioedema). Despite a very similar clinical presentation among subtypes, the differential diagnosis is limited by the difficulty to identify bradykinin-mediated PA and the lack of specific biomarkers. Objectives To report the clinical and genetic features of Brazilian patients with PA. Methods Brazilian patients referred from 50 centers were diagnosed on the basis of clinical symptoms, C1 inhibitor (C1-INH) and C4 plasma measurements, and DNA sequencing of genes associated with hereditary angioedema. Results We characterized 92 patients with acquired angioedema and 425 with HAE: 125 with C1-INH deficiency, 180 with F12 mutations, and 120 of unknown cause. Thirty-one different mutations were identified in SERPING1 and 2 in F12, in addition to 2 mutations of uncertain significance in the ANGPT1 gene. The molecular diagnosis was decisive for 34 patients with HAE without family history, and for 39% of patients with inconsistent biochemical measurements. The median delay in diagnosis was 10 years, with a maximum of 18 years for HAE with C1-INH deficiency. Androgens and tranexamic acid were the most used drugs for long-term prophylaxis in all the PA subtypes, and they were used on demand by 15% of patients. Only 10% of patients reported the use of specific medication for HAE during attacks. Conclusions Our analysis exposes a broad picture of PA diagnosis and management in a developing country. Complement measurements presented considerable inconsistencies, increasing the diagnosis delay, while patients with PA with normal C1-INH remain with an inaccurate diagnosis and unspecific treatment.

Would STAT1 GOF prevent severe forms of COVID-19?To the Editor:As the world faces the current SARS-CoV-2 pandemic, the scientific community struggles to answer questions about the disease that have not been fully clarified yet. It is well known that individuals with certain chronic diseases are at higher risk of having worse prognosis when infected with this virus. Although the risk of a severe disease is still a matter of conjecture in subjects with Inborn errors of Immunity (IEI), these patients may present more COVID-19 complications than the general population, either by community acquired or nosocomial infection1.In our immunology referral clinic at the Federal University of Sao Paulo (UNIFESP), so far, 16 IEI patients have been diagnosed with COVID-19, with a large spectrum of presentation, ranging from mild disease to severe acute respiratory syndrome and death. One of them, however, had a favorable outcome, with no complications, after being infected with the SARS-CoV-2, despite his several serious comorbidities.We report the case of an 11- year -old boy, diagnosed with Type 1 Diabetes Mellitus at the age of 3 years. At that time, he presented persistent watery diarrhea, 3 to 4 episodes a day. One year later, productive cough, persistent fever, conjunctival hyperemia and generalized lymph node enlargement emerged. Histoplasma sp. was isolated in ocular secretion. Acute Disseminated Histoplasmosis (pulmonary, ocular and ganglionic) was diagnosed and he received Itraconazole for one year.In 2018, at the age of 9 years, we started to follow him at our immunology clinic. He received all vaccines for his age with no adverse events. The family reported recurrent skin infections, repeated pneumonia, mucocutaneous and esophageal candidiasis, and arthralgia. He presented hepatomegaly and failure to thrive. The main diagnostic hypothesis was a disease of immune dysregulation. Screening for inborn errors of immunity and inflammatory lab tests were performed. White blood cell count, immunophenotyping and lymphocyte proliferation, serum immunoglobulins and dihydrorodamine (DHR) assay were in normal range. HIV serologies were negative. Whole exome sequencing was performed and the variant c.1675G> C (de novo variant) appeared in the STAT1 gene (Figure 1)3, in heterozygosis. To date, no data on this genetic variant has been published. This new finding is probably considered pathogenic and, due to the patient’s clinical characteristics, STAT1-GOF is very likely to be the diagnosis of our boy.

Introduction: Ataxia-Telangiectasia (A-T) is a multi-system disorder that may be associated with endocrine changes, oxidative stress in addition to inflammation. Studies suggest that selenium (Se) is a trace element related to protection against damage caused by oxidative stress; it is postulated that adequate consumption reduces the risk of some chronic diseases. Objective: To describe the concentrations of Se and glutathione peroxidase (GPx) in patients with A-T, to relate them to markers of the lipid profile. Methods: We evaluated, through a controlled cross-sectional study, 22 A-T patients matched by sex and age with healthy individuals, conjointly evaluating: nutritional status, food intake, serum selenium, glutathione peroxidase (activity), lipid metabolism biomarkers, inflammation and lipid. Results: The median age in the A-T group was 12.2 years. A-T patients had greater impairment of lean body mass and GPx activity as well as lower abdominal circumference. A more atherogenic lipid profile was observed with higher concentrations of total cholesterol, non-HDL cholesterol, LDLox, Apo B, Apo B / Apo A-1 and LDL / HDL ratio; while a lower value was observed in the Apo A-1 / HDL ratio. It was also in the A-T group that statistical difference was detected in the three markers of liver function AST, ALT and GGT. In regard to food intake, A-T patients had lower values ​​of carbohydrate, protein, monounsaturated fat, trans fat, and Se. Conclusion: The study showed cardiovascular risk in A-T patients. A-T patients appear to be at increased risk of reduced nutritional status, impaired liver function, dyslipidemia and inflammation.

Asthma is reported as one of the most common chronic diseases in childhood, impairing the quality of life of patients and their families and incurring high costs to the healthcare system and society. Despite the development of new drugs and the availability of international treatment guidelines, asthma is still poorly controlled, especially in Latin America. Original and review articles on asthma control or epidemiology with high levels of evidence have been selected for analysis among those published in PubMed referenced journals during the last 20 years, using the following keywords: “asthma control” combined with “Latin America”, ” epidemiology”, “prevalence”, “burden”, “mortality”, “treatment and unmet needs”, “children”, “adolescents”, and “infants”. There was a high prevalence and severity of asthma during the period analyzed, especially in children and adolescents. Wheezing in infants was a significant reason for seeking medical care in Latin American health centers. Moreover, the frequent use of quick-relief bronchodilators and oral corticosteroids by these patients indicates the lack of a policy for providing better care for asthmatic patients, as well as poor asthma control. Among adults, studies document poor treatment and control of the disease, as revealed by low adherence to routine anti-inflammatory medications and high rates of emergency care visits and hospitalization. In conclusion, although rare, studies on asthma control in Latin America repeatedly show that patients are inadequately controlled and frequently overestimate their degree of asthma control according to the criteria used by international asthma treatment guidelines. Additional education for doctors and patients is essential for adequate control of this illness, and therefore also for reduction of the individual and social burden of asthma.

The clinical history is of importance in the investigation of allergic diseases but does have limitations. Many allergic conditions will be over-diagnosed if anamnesis alone is used for diagnostic criteria. Serum total immunoglobulin E (TIgE) quantification, as well as panels containing allergens prevalent in the studied population, may serve as screening tests and facilitate the diagnosis of allergic disease or its exclusion. We assessed the positivity of two versions of these tests, Phadiatop Europe® (PhEU) and Phadiatop Infant® (PhInf), as well as total IgE (TigE) values in patients with a medical diagnosis of allergic disease and non-allergic individuals. Methods A cross-sectional study performed in eleven Brazilian pediatric allergy centers with patients divided into groups according to the primary condition and a group of assessed control subjects. They were submitted to TIgE measurement and screening tests (PhEu and PhInf). Results TIgE mean serum levels were significantly higher among allergic patients, especially those with asthma/rhinitis or atopic dermatitis. The positivity of the screening tests, considering the total population, was 63.8% for PhEU and 72.6% for PhInf. These increased when we evaluated only the allergic subjects. The concordance index of the two tests was Kappa = 0.7 and higher among those of greater age. Conclusions In the assessed population, there were significantly higher levels among those with positive screening tests and PhInf showed better performance in the identification of sensitized individuals, regardless of age. This is the first study to evaluate Phadiatop and Phadiatop Infant in the same population.

Drug-induced anaphylaxis (DIA) is a severe, life-threatening reaction occurring after drug exposure. It is an important cause of anaphylaxis and accounts for up to one third of drug hypersensitivity reactions. As in other anaphylaxis reactions, immunoglobulin E (IgE) has an important role in its mechanism, but other non-immunological reactions may also occur in DIA. Cutaneous and respiratory symptoms are present in a majority of patients, and cardiovascular events are more common in elderly patients. A complete work up is recommended not just to offer safe alternatives, but also to avoid incorrect labeling of patients as allergic to drugs. The investigation includes in vitro tests when available, followed by skin prick and intradermal tests. Although provocation tests are still considered the “gold standard” for the diagnosis of drug allergy, in DIA, the risk versus benefit ratio must be analyzed. Non-steroid anti-inflammatory drugs and antibiotics are the drug classes more frequently involved. Neuromuscular blocking agents, chemotherapeutic drugs, and biologics are commonly related to reactions in a hospital setting. Prevention measures include an individualized education plan, with recommendations to avoid the culprit drug and potential cross-reactive medications. In selected patients, desensitization can induce a temporary state of tolerance. Protocols are available and can be adapted for drugs used in different situations, from cancer treatment to enzyme replacement therapy.

Fabry disease is a rare lysosomal storage disorder, inherited in an X-linked manner. It is characterized by the deficiency of the enzyme alpha-galactosidase, leading to a buildup of glycosphingolipids in the cells. Angiokeratoma is one of the cutaneous manifestations of this condition, and it helps making the diagnosis. The typical site involves the genital area in men and lumbosacral, buttocks and trunk region in both sexes. We report a case of genital angiokeratoma in a woman with Fabry disease. The diagnosis is through molecular analysis and, when made early, starting treatment reduces the morbidity and mortality of the disease. Thus, the dermatologist has an important role in the identification of angiokeratoma as a cutaneous marker, and the knowledge of its different presentations is essential for the early diagnosis and management of Fabry disease.

BioMarin Pharmaceutical Inc. Shire Genzyme BioMarin Background: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme (R), BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.Methods: Data from patients who initiated treatment at

Objective The aim of this study was to evaluate pulmonary complications in patients with primary antibody deficiency (X-linked agammaglobulinaemia [XLA] and common variable immunodeficiency [CVID]). Methods Thirty patients over six years of age regularly followed in a reference out-patient clinic on primary immunodeficiency were studied. All of them have been treated with intravenous immunoglobulin (IVIG) replacement therapy. Pulmonary complications were evaluated analysing clinical data (medical records review), lung function test (spirometry) and pulmonary imaging (chest computed tomography [CCT]). Results Patients with normal CCT (N=14) and those with abnormal CCT (N=16) have shown no differences regarding the age at onset of symptoms, age of diagnosis, and duration of IVIG treatment. The mean number of pneumonia episodes before IVIG replacement was significantly higher among patients with abnormal CCT (4 vs 7 episodes, p=0.008). CCT abnormalities observed in 16 patients were: bronchiectasis (12/16); peribronchial thickening (3/16); air trapping (5/16); lung volume reduction (4/16); atelectasis (2/16), follicular bronchiolitis and ground-glass abnormality (2/16) and parenchyma nodule (1/16). Lung function tests showed ventilatory disturbance in 18/30: obstructive pattern in 38.8%, restrictive pattern in 44.4%, and mix pattern in 16.7%. There were no significant differences in lung function between those with and without CCT abnormalities. Negative significant correlations were observed between lung function and number of episodes of pneumonia. Chronic persistent cough was associated with a reduction in lung function. Conclusions Pulmonary complications are not rare in patients with antibody deficiencies and they must be monitored.

Introduction Asthma is an inflammatory disorder of the airways associated with bronchial hyperresponsiveness, airway obstruction, and increased mucus production, with a predominance of type 2 immune response (Th2). According to the hygiene hypothesis, exposure to environmental bacterial lipopolysaccharide (LPS) may induce a type 1 immune response (Th1), modulating the development of asthma. Objective In this study we investigated cytokine production by peripheral blood mononuclear cells (PBMC) from children and adolescents with severe asthma, in response to LPS stimulation in vitro. Materials and methods 26 children were selected: 13 severe asthmatics and 13 healthy controls, aged between 5 and 18 years. They were evaluated through routine medical history, physical examination and lung function test to diagnose severe asthma. Allergy status was confirmed by skin prick test and specific IgE assay. We collected blood samples to analyse in vitro LPS-induced cytokines release by PBMC. Results PBMC from severe asthmatic children produced lower levels of IL-12p70 in basal conditions and after 12 and 24 h stimulation with LPS compared to healthy controls. PBMC from severe asthmatic children produced lower levels of IL-4 after 24 h LPS stimulation compared to healthy controls. PBMC from severe asthmatic children produced more levels IL-17 and IL-10 after stimulus with LPS compared to healthy controls. The release of IFN-γ, IL-5 and TNF-α by PBMC from severe asthmatic children was similar to healthy controls. Conclusion Our results demonstrate that LPS directly influence the cytokine profile of PBMC in children with severe asthma. These observations may be potentially helpful in developing new treatment strategies.

Background MPS is a group of metabolic diseases caused by deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAG). Recurrent respiratory infections, sleep disturbances, upper and lower airway obstruction are frequently reported in MPS’ patients. However, cellular accumulation of GAG fragments leading to progressive multi-system manifestations can clutter homeostasis also modify the function of other cellular components, their signals and produce substances. The aim of study is to evaluate immunologically MPS’ patients to clarify why they are prone to infections.

Results After 28 days the use of GB and 20 days of grafting, she had morbilliform rash, fever (39C), cervical and inguinal adenopathy. CBC was performed: hemoglobin 10,3g/dl, leukocyte 14,900/mm3, neutrophils 58.9%, eosinophils 16.4% (2,443), lymphocytes 10% and monocytes 3.1%. Platelets were normal. ALT 200 U/L (up to 55), AST 180U/L (up to 34), creatinine 1.8 mg/dl (up to 1). Previous examinations showed no changes except for leukocytosis with a left shift. As European Registry of Severe Cutaneous Adverse Reactions (SCAR) to Drugs and Collection of Biological Samples, the patient had score 6 (definite case). GB was removed and the patient was treated with methylprednisolone 120 mg / day IV for 3 days. Thereafter, the medication was continued at a dose of 60mg/day for 5 days. After 72 hours, the patient was afebrile with improved lymph node, the rash, renal and hepatic parameters. Gradual withdrawal of corticosteroids had done because the patient had significant eosinophilia (≥ 1500/mm3), prednisone 30mg for 7 days, then 20 mg for 7 days, 10mg for 7 days and maintained 5mg for 20 days. After three months, the patient showed eosinophilia but no acute relapse of the condition.

Background We aimed to identify factors associated with recurrent wheezing (RW) in infants in the first year of life living in the Southern region of Sao Paulo city and participating in the “ Estudio Internacional de Sibilancias en Lactantes (EISL)” – phase 3 (P3). Methods 1335 parents of infants who were attended in primary care health units in the Southern region of Sao Paulo city from 2009 to 2010 answered the EISL-P3 written questionnaire. The wheezing group was stratified in accordance to the frequency of wheezing episodes as occasional wheezing (OW, less than three episodes), or RW (three or more episodes). Wheezing-associated factors were evaluated using multivariate analysis and were expressed as odds ratio (OR) and 95% confidence interval (95%CI). Results The most relevant factors related to OW were pneumonia (OR = 3.10, 95%CI = 1.68–5.73), hospitalisation due to pneumonia (OR = 2.88, 95%CI = 1.26–6.56) and recurrent upper respiratory infection (URI, OR = 1.87, 95%CI = 1.25–2.81). Regarding RW, recurrent URI (OR = 5.34, 95%CI = 3.83–7.45), pneumonia (OR = 4.06, 95%CI = 2.87–5.74) and asthmatic siblings (OR = 3.02, 95%CI = 1.67–5.45) were the most significantly associated factors. Conclusions In the present study, we found that recurrent URI, positive history of pneumonia and familiar history of asthma were the most relevant factors associated with RW. The precocious knowledge of these factors can enable the identification of the probable asthmatic infants and can improve both prevention strategies and treatment of these patients.