Cockroach allergy and asthma in a 30-year-old man.

A growing body of evidence has implicated allergens derived from cockroaches as an important environmental factor that may aggravate asthma in sensitized persons. We present the case of a 30-year-old man with asthma and a cockroach allergy. Allergy skin testing confirmed hypersensitivity to cockroach extract, and a home visit revealed visual evidence of infestation and the presence of Bla g 1 German cockroach allergen in vacuumed dust. As is typical of patients with a cockroach allergy and asthma, multiple factors in addition to cockroach allergen appeared to aggravate the patient's asthma. A multimodality therapeutic regimen, which included medications as well as cleaning of the home, integrated pest management, and professional application of chemical controls, resulted in substantial clinical improvement. The pathophysiology, epidemiology, and clinical features of cockroach-allergic asthma are reviewed, and an approach to diagnosis and management is suggested

Mechanisms of Allergen-Antibody Interaction of Cockroach Allergen Bla g 2 with Monoclonal Antibodies That Inhibit IgE Antibody Binding

BACKGROUND: Cockroach allergy is strongly associated with asthma, and involves the production of IgE antibodies against inhaled allergens. Reports of conformational epitopes on inhaled allergens are limited. The conformational epitopes for two specific monoclonal antibodies (mAb) that interfere with IgE antibody binding were identified by X-ray crystallography on opposite sites of the quasi-symmetrical cockroach allergen Bla g 2. METHODOLOGY/PRINCIPAL FINDINGS: Mutational analysis of selected residues in both epitopes was performed based on the X-ray crystal structures of the allergen with mAb Fab/Fab' fragments, to investigate the structural basis of allergen-antibody interactions. The epitopes of Bla g 2 for the mAb 7C11 or 4C3 were mutated, and the mutants were analyzed by SDS-PAGE, circular dichroism, and/or mass spectrometry. Mutants were tested for mAb and IgE antibody binding by ELISA and fluorescent multiplex array. Single or multiple mutations of five residues from both epitopes resulted in almost complete loss of mAb binding, without affecting the overall folding of the allergen. Preventing glycosylation by mutation N268Q reduced IgE binding, indicating a role of carbohydrates in the interaction. Cation-π interactions, as well as electrostatic and hydrophobic interactions, were important for mAb and IgE antibody binding. Quantitative differences in the effects of mutations on IgE antibody binding were observed, suggesting heterogeneity in epitope recognition among cockroach allergic patients. CONCLUSIONS/SIGNIFICANCE: Analysis by site-directed mutagenesis of epitopes identified by X-ray crystallography revealed an overlap between monoclonal and IgE antibody binding sites and provided insight into the B cell repertoire to Bla g 2 and the mechanisms of allergen-antibody recognition, including involvement of carbohydrates

Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis

Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the “Associação Brasileira de Alergia e Imunologia (ASBAI)” and the “Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)” has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

Asthma prevalence and risk factors in schoolchildren of the city of São Paulo, Brazil

OBJETIVO: Analisar a prevalência de asma e possíveis fatores de risco associados. MÉTODOS: Estudo transversal, integrante do International Study of Asthma and Allergies in Childhood. Participaram 561 escolares de seis a sete anos de idade, provenientes de 35 escolas públicas da cidade de São Paulo, escolhidas por sorteio, em 2002. A amostra incluiu 168 asmáticos e 393 não asmáticos, que responderam questionário constituído por 33 questões referentes a dados pessoais, familiares e ambientais. A associação entre asma e fatores de risco foi avaliada pela análise de regressão logística, considerando-se nível de significância estatística de 5%. RESULTADOS: Entre os escolares, 31,2% referiam sibilos nos 12 meses anteriores à entrevista. Os fatores de risco significativamente associados à asma foram: sexo masculino (OR=2,4;IC 95%: 1,4;4,2), mãe fumante no primeiro ano de vida (OR=2,0; IC 95%: 1,1;3,8), presença de eczema em locais característicos (OR=3,0; IC 95%:1,2; 7,6) e rinoconjuntivite (OR=2,4;IC 95%: 1,2; 4,8). CONCLUSÕES: A prevalência de asma na região estudada foi elevada e os fatores de risco relacionados foram: sexo masculino, sintomas de rinoconjuntivite no último ano, mãe fumante no primeiro ano de vida e presença de eczema em locais característicos.OBJECTIVE: To assess asthma prevalence and potential risk factors associated. METHODS: Cross-sectional study part of the International Study of Asthma and Allergies in Childhood. A total of 561 schoolchildren aged 6-7 years from 35 public schools in the city of São Paulo (Southeastern Brazil) were drawn to participate in the study, in 2002. The sample consisted of 168 asthmatic and 393 non-asthmatic children who answered a questionnaire comprising 33 questions on personal, family and environmental information. The association between asthma and the risk factors studied was assessed by logistic regression analysis at a 5% statistical significance. RESULTS: Among the schoolchildren studied, 31.2% reported wheezing in the 12 months preceding the interview. The following risk factors were significantly associated with asthma: male gender (OR=2.4; 95% CI: 1.4;4.2), maternal smoking in the child's first year of life (OR=2.0; 95% CI: 1.1;3.8), eczema on characteristic body areas (OR=3.0; 95% CI: 1.2;7.6) and rhinoconjunctivitis (OR=2.4; 95% CI: 1.2;4.8). CONCLUSIONS: Asthma prevalence in the study area was high and the risk factors identified were male gender, rhinoconjunctivitis in last year, maternal smoking in the child's first year of life and eczema on characteristic body areas

Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients

Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: A randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Endotoxins are ubiquitously present in the environment and constitute a significant component of ambient air. These substances have been shown to modulate the allergic response, however a consensus has yet to be reached whether they attenuate or exacerbate asthmatic responses. The current investigation examined whether reducing the concentration of lipopolysaccharide (LPS) in a house dust extract (HDE) containing high concentrations of both cockroach allergens <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and LPS would attenuate asthma-like pulmonary inflammation.</p> <p>Methods</p> <p>Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA. Multiple parameters of asthma-like pulmonary inflammation were measured.</p> <p>Results</p> <p>Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and IgG1 were significantly reduced, however no change in CRA-specific IgE was detected. In HDE mice, plasma IgG2a levels were similar to naïve mice, while LPS-reduced HDE mice had significantly greater concentrations. Reduced levels of LPS in the HDE did not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine challenge. <it>Conclusion: </it>These data show that reduction of LPS levels in the HDE does not significantly protect against the severity of asthma-like pulmonary inflammation.</p