Gesmar Rodrigues Silva Segundo

Serum and Salivary IgE, IgA, and IgG4 Antibodies to Dermatophagoides pteronyssinus and Its Major Allergens, Der p1 and Der p2, in Allergic and Nonallergic Children

Allergic rhinitis (AR) is a public health problem with high prevalence worldwide. We evaluated levels of specific IgE, IgA, and IgG4 antibodies to the Dermatophagoides pteronyssinus (Dpt) house dust mite and to its major allergens (Der p1 and Der p2) in serum and saliva samples from allergic and nonallergic children. A total of 86 children were analyzed, from which 72 had AR and 14 were nonallergic healthy children. Serum IgE and serum/salivary IgG4 levels to Dpt, Der p1, and Der p2 were higher in allergic children whereas serum/salivary IgA levels to all allergens were higher in nonallergic children. IgE levels positively correlated with IgG4 and IgA to all allergens in allergic children, while IgA levels negatively correlated with IgG4 to Dpt and Der p1 in nonallergic children. In conclusion, mite-specific IgA antibodies predominate in the serum and saliva of nonallergic children whereas mite-specific IgE and IgG4 are prevalent in allergic children. The presence of specific IgA appears to have a key role for the healthy immune response to mucosal allergens. Also, specific IgA measurements in serum and/or saliva may be useful for monitoring activation of tolerance-inducing mechanisms during allergen specific immunotherapeutic procedures, especially sublingual immunotherapy.

Clinical characteristics and sensitivity to food and inhalants among children with eosinophilic esophagitis

BackgroundTo 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.ResultsPatients (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.ConclusionsThe 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.

Mite and pet allergen exposure in Brazilian private cars.

BACKGROUNDnThe role of mite and pet allergens in the development of allergic diseases has been recognized for many years.nnnOBJECTIVEnTo determine mite (Dermatophagoides pteronyssinus [Der p 1] and Dermatophagoidesfarinae [Der f 1]), cat (Felis domesticus [Fel d 1]), and dog (Canis familiaris [Can f 1]) allergen levels in Brazilian private cars.nnnMETHODSnMite, cat, and dog allergens were measured in dust samples collected from 60 upholstered seats of private vehicles using enzyme-linked immunosorbent assays.nnnRESULTSnMean levels of Der p 1 (0.24 microg/g of dust; range, 0.06-2.05 microg/g of dust) and Der f 1 (0.29 microg/g of dust; range, 0.06-2.07 microg/g of dust) were extremely low in most dust samples analyzed. In contrast, sensitizing mean levels of Can f 1 (1.51 microg/g of dust; range, 0.14-30.96 microg/g of dust) and Fel d 1 (0.43 microg/g of dust; range, 0.02-5.75 microg/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 microg/g of dust) than in those without pets (0.57 microg/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.nnnCONCLUSIONSnPrivate 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.

Spirometric parameters and levels of interferon gamma and IL-5 in induced sputum from patients with allergic rhinitis or asthma.

BACKGROUNDnThis 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.nnnMETHODSnThirty-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.nnnRESULTSnSignificant 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.nnnCONCLUSIONnSpirometric 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.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.”

Paternal gonadal mosaicism as cause of a puzzling inheritance pattern of activated PI3-kinase delta syndrome

Birth defects caused by de novo chromosomal abnormalities resulting in single-gene defects occur in approximately 5% of all live births.1 Affected offspring have a broad range of illnesses, including primary immunodeficiency diseases, a genetically heterogeneous group of disorders presenting with a clinical spectrum of mild to severe infections, often complicated by autoimmunity and malignancies.2 Most primary immunodeficiency diseases are monogenic diseases with a Mendelian inheritance pattern.2 Recently, heterozygous gain-of-function mutations in PIK3CD, encoding the catalytic p110d subunit of phosphatidylinositol 3-kinase (PI3K), were identified in patients presenting with recurrent respiratory tract infections, hepatosplenomegaly, polyadenopathy, CD4 lymphopenia, and decreased numbers of class-switched memory B cells, a phenotype referred to as activated PI3K delta syndrome type 1 (APDS1).3,4 Patients with APDS1 exhibit increased basal and stimulation-dependent activation of the AKT-mTOR pathway. Similar clinical findings and PI3K signaling activation have been observed in patients with heterozygous mutations in the PIK3R1 gene, encoding the regulatory subunit of PI3K, referred to as APDS2.5 We identified a kinship that included 3 half-siblings with symptoms typical for APDS1. The index case (II.4 in Fig 1A) had 10 episodes of pneumonia, 2 episodes of sepsis, several upper respiratory infections, and oral moniliasis within the first year of life. He subsequently developed hepatosplenomegaly, lymphadenopathy, and an axillary abscess owing to Candida albicans. At 3 years of age, laboratory investigation showed increased immunoglobulin (Ig) M (368 mg/dL) and IgG (1,450 mg/dL) levels, normal IgA level (107 mg/dL), low CD4 (330/mm3) and increased CD8 (1,229/mm3) counts, and low CD19 B cells (17/mm3). IgG subclasses showed normal absolute levels of IgG1 (1,020 mg/dL), IgG2 (79.0 mg/dL), IgG3 (78.3 mg/dL), and IgG4 (28.1 mg/dL); however, their ratio showed a proportional decrease of IgG2. Based on the clinical symptoms, APDS1 was suspected and a heterozygous PIK3CD hotspot mutation (c.3061G/A, p.E1021K) was identified by Sanger sequencing. He was treated with intravenous immunoglobulin, cotrimoxazole prophylaxis, and rapamycin, resulting in marked decrease of hepatosplenomegaly and alleviation of his other symptoms. The patient’s father (I.4), a truck driver, reported that in addition to the index case, he had 4 additional children with 3 other women living in different Brazilian cities along his truck route and that 2 of these children (II.4 and II.5) had symptoms similar to the index case (Fig 1A). Of his 5 children, 1 had died at 3 years of age (II.1) with

Low efficacy of atopy patch test in predicting tolerance development in non-IgE-mediated cow's milk allergy

BACKGROUNDnThe 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 cows milk APT preparations to predict oral tolerance in children with previous non-IgE-mediated cows milk allergy (CMA) diagnosis.nnnMETHODSnThirty-two patients non-IgE-mediated CMA diagnosed by oral food challenge (OFC) were enrolled to perform APT with three different cows milk preparations (fresh, 2% in saline solution, 2% in petrolatum) and comparing with a new OFC after at least three months of diet exclusion.nnnRESULTSnOnly six (18.7%) subjects presented positive OFC to cows 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.nnnCONCLUSIONnCows 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.