Adriana S. Moreno

A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family

To cite this article: Ferraro MF, Moreno AS, Castelli EC, Donadi EA, Palma MS, Arcuri HA, Lange AP, Bork K, Sarti W, Arruda LK. A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family.Allergy 2011; 66: 1384–1390.

Targeting the T Helper 2 Inflammatory Axis in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects up to 25% of children and 10% of adults. The skin of patients with moderate to severe AD is characterized by significant barrier disruption and T helper 2 (Th2)-driven inflammation, which are thought to play a significant role in the pathogenesis of AD. Current management of AD is aimed at suppressing the inflammatory response and restoring the barrier function of the skin, reducing exacerbations, and preventing secondary skin infections. Combinations of treatment strategies are used to alleviate the symptoms of the disease; however, resolution is often temporary, and long-term usage of some of the medications for AD can be associated with significant side effects. Antibody therapies previously approved for other inflammatory diseases have been evaluated in patients with AD. Unfortunately, they have often failed to result in significant clinical improvement. Monoclonal antibodies and novel small molecules currently in development may provide more consistent benefit to patients with AD by specifically targeting the immune and molecular pathways important for the pathogenesis of AD. Here we review the state-of-the-art therapeutics targeting the Th2 axis in AD.

Coagulation Factor XII Gene Mutation in Brazilian Families with Hereditary Angioedema with Normal C1 Inhibitor

Background: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare disorder. Mutations of the gene encoding coagulation factor XII have been identified in a subset of patients with this condition. Our aim was to investigate mutations in the F12 gene in patients with HAE with normal C1-INH from Brazil. Methods: We studied 5 Brazilian families with index female patients who presented with recurrent angioedema with normal C1-INH and C4 levels. Genomic DNA was isolated from whole blood and PCR was performed. Mutations were detected by the sequencing of exon 9 of the F12 gene and allelic discrimination. Results: The c.983C>A (p.Thr328Lys) mutation was identified in 16 subjects, from 4 of the 5 families studied, including 8 patients with symptoms of HAE with normal C1-INH (87.5% women) and 8 subjects asymptomatic for HAE (25% women). Mean age at onset of symptoms among the FXII-HAE patients was 13.8 years (range 6-25 years). Recurrent abdominal pain (100%) and subcutaneous angioedema (87.5%) were the most frequent clinical presentations. Two patients presented with associated laryngeal edema. In keeping with previous observations in patients with both C1-INH-HAE and HAE with normal C1-INH, all 7 women with FXII-HAE reported triggering or worsening of symptoms upon intake of estrogen-containing oral contraceptives and/or pregnancy. Conclusions: We report for the first time in Brazil a mutation in the F12 gene as a likely cause of HAE with normal C1-INH in patients with recurrent attacks of angioedema and/or abdominal pain. A higher frequency of abdominal pain attacks and onset of symptoms at a younger age were observed among Brazilian patients when compared to those from other parts of the world.

Alérgenos recombinantes: papel no diagnóstico e na imunoterapia alérgeno-específica

RESUMO Nos ultimos 30 anos tem havido um avanco notavel na identificacao, purificacao e expressao recombinante de alergenos relevantes das mais variadas fontes, incluindo acaros, insetos, ma‑ miferos, polens, alimentos, fungos, latex e outras fontes. Estes avancos resultaram na utilizacao crescente de alergenos purificados, naturais ou recombinantes, para melhorar o diagnostico de alergia pelos metodos que dispomos, incluindo os testes cutâneos de hipersensibilidade imediata, e os metodos in vitro para medida de anticorpos IgE especificos, como ImmunoCAP, ImmunoCAP- ISAC, ELISA e MARIA. Mais recentemente, o uso de alergenos recombinantes de polen de betula (rBet v 1) e de gramas (coquetel de 5 alergenos) em imunoterapia foi relatado como seguro e eficaz, com resultados comparaveis aos obtidos usando extratos naturais, em pacientes com rinoconjuntivite alergicos a polens. No presente artigo, apresentamos revisao atualizada do uso de alergenos recombinantes em diagnostico de alergia e em imunoterapia alergeno-especifica, incluindo novas estrategias de imunoterapia. Focalizamos na avaliacao critica de estudos que investigaram sensibilidade, especificidade, reatividade cruzada e valor prognostico de metodos diagnosticos com uso de alergenos recombinantes versus extratos naturais; nas recomendacoes atuais para o uso destes novos metodos na pratica clinica; e na revisao de estudos clinicos com imunoterapia usando alergenos recombinantes realizados ate o momento.

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.

Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families.

BACKGROUND Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare condition with clinical features similar to those of HAE with C1-INH deficiency. Mutations in the F12 gene have been identified in subsets of patients with HAE with normal C1-INH, mostly within families of European descent. OBJECTIVES Our aim was to describe clinical characteristics observed in Brazilians from 42 families with HAE and F12 gene mutations (FXII-HAE), and to compare these findings with those from other populations. METHODS We evaluated a group of 195 individuals, which included 102 patients clinically diagnosed with FXII-HAE and their 93 asymptomatic relatives. RESULTS Genetic analysis revealed that of the 195 subjects, 134 individuals (77.6% females) carried a pathogenic mutation in F12. The T328K substitution was found in 132 individuals, and the c.971_1018+24del72 deletion was found in 2 patients. The mean age at onset of symptoms in patients with FXII-HAE was 21.1 years. The most common symptoms were subcutaneous edema (85.8% of patients), abdominal pain attacks (69.7%), and upper airway edema (32.3%). Of male individuals carrying F12 mutations, 53.3% (16 of 30) were symptomatic. Compared with reports from Europe, fewer female patients (68.6%) reported an influence of estrogen on symptoms. CONCLUSIONS Our study included a large number of patients with FXII-HAE, and, as the first such study conducted in a South American population, it highlighted significant differences between this and other study populations. The high number of symptomatic males and patients with estrogen-independent FXII-HAE found here suggests that male sex and the absence of a hormonal influence should not discourage clinicians from searching for F12 mutations in cases of HAE with normal C1-INH.

Bronchial hyperreactivity induced by tropomyosins from cockroach and shrimp: a mouse model to study in vivo cross-reactivity

Methods Balb/c mice, 4 to 6 weeks-old, were sensitized twice with 50μg of rPer a 7 or nLit v 1 intraperitoneally with 1 mg alum, and challenged with 50μg of rPer a 7 or nLit v 1 intranasally for three days. A group was sensitized with rPer a 7 and challenged with nLit v 1 under same conditions. Controls received saline on same days. Twenty-four hours after the last challenge, mice were ventilated with FlexiVent, and in vivo bronchial hyperresponsiveness was evaluated with increased doses of inhaled methacholine (6.25, 12.5, 25 and 50mg/ml). After ventilation, bronchoalveolar lavage fluid (BALF) was collected and cell counts were performed.

A systematic intervention for assistance of patients with asthma in Brazil: partnership between university and public health system

Methods A group of 16 allergists/immunologists developed a capacitating program in 11 Public Health Units in the city of Ribeirao Preto, Brazil. The program comprised lectures on asthma and hands-on training on spirometry and use of inhalation devices; production of didactic material; and development of a protocol on management of asthma. Spacers and spirometry were provided. Each researcher visited one Health Unit 2-4 times a month, to accompany the non-specialist on patients’ visits to the clinic, perform case discussions, and deliver short lectures to the health professionals. Records of asthma medications provided to patients upon physicians’ prescription in the North Region were compared to those from three other Regions with no intervention.

Angioedema hereditário e outras formas de angioedema por bradicinina: atualização no diagnóstico e tratamento

ABSTRACTRESUMO Angioedema hereditario e outras formas de angioedema por bradicinina: atualizacao no diagnostico e tratamento 1 Universidade Presidente Antonio Carlos (Unipac), Araguari, MG. 2 Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo. Artigo de Revisao Hereditary angioedema and other forms of bradykinin-mediated angioedema: update on diagnosis and treatment Maria Fernanda Ferraro, MD, PhD 1 ; L. Karla Arruda, MD, PhD 2 ; Luana S. M. Maia, MSc 2 ; Adriana S. Moreno, PhD 2 Angioedema e definido como edema que ocorre em areas bem delimitadas do tecido subcu-tâneo e submucoso, consequente ao aumento da permeabilidade capilar local causada por mediadores vasoativos. Em geral acomete extremidades, face, vias aereas superiores e tratos gastrointestinal e geniturinario. Ha dois mediadores amplamente reconhecidos na patogenese do angioedema: histamina e bradicinina, com repercussoes clinicas distintas. O angioedema histaminergico e geralmente associado a urticaria e tem boa resposta ao tratamento com anti-histaminicos, corticosteroides e adrenalina. Ja o angioedema por bradicinina tem duracao mais prolongada (36 a 72 horas), envolve mais frequentemente o trato gastrointestinal e nao responde ao tratamento convencional com anti-histaminicos, corticosteroides e adrenalina. Suspeita-se de angioedema mediado por bradicinina quando ha angioedema recorrente, nao associado a urticaria, que pode ser hereditario ou adquirido. O nonapeptideo bradicinina e um potente mediador de vasodilatacao e aumento da permeabilidade vascular, particularmente em venulas pos-capilares, que produz seus efeitos atraves da estimulacao dos receptores B2 ligados a proteina-G. Neste artigo de revisao, temos por objetivo fazer uma atualizacao em diagnostico diferencial e tratamento das diferentes formas de angioedema mediado por bradicinina: an-gioedema por inibidores da enzima conversora da angiotensina (iECA) e outros farmacos que podem diminuir o metabolismo da bradicinina; angioedema hereditario (AEH) por mutacoes nos genes

Health outcomes, education, healthcare delivery and quality – 3051. Profiles of diagnosis and treatment of asthma in the public health system in Brazil

Health outcomes, education, healthcare delivery and quality – 3051. Profiles of diagnosis and treatment of asthma in the public health system in Brazil Janaina M Melo, Adriana S Moreno, Virginia PL Ferriani, Elcio Vianna, Marcos Borges, Persio Roxo Jr, Ana Carla S Araujo, Luane M Mello, Rosa Ferreira, Jorgete M Silva, Patricia Stefanelli, Marcos R Goncalves, Larissa P Oliveira, Andrea Cetlin, Luana B Queiroz, Rosangela Villela, Davi C Aragon, L Karla Arruda