Plasma Kallikrein Role in Hereditary Angioedema: Genetics and Functional Analysis.

• Grant number: 11/24142-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2012
• End date: June 30, 2016
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Bosco Pesquero
• Grantee: Camila Lopes Veronez
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 13/26117-1 - B2 kinin receptor overexpression rat as hereditary angioedema animal model, BE.EP.DR

Abstract

The hereditary angioedema (HAE) is characterized by repetitive episodes of painfuledemas and discomfort which affects mainly the upper and lower extremities, gastrointestinaltract, genitals and face, and it can lead to death by asphyxiation in swelling of upperrespiratory tract. The HAE is an autosomal-dominant disorder resulting from mutations in theC1 inhibitor that result in its abnormal levels or functionality (HAE Type I and II,respectively) or the result of other disorders (HAE Type 3) leading to an overproduction ofbradykinin (BK), the peptide responsible for edema. C1-INH is the main physiologic inhibitorof the contact system factor XII (FXII) and plasma kallikrein (huPK), which is responsible forBK release.The aim of this project is to study huPK role in HAE, analyzing its genetic andfunctional alterations in HAE patients, correlating with different patient's symptoms.Thus, genomic DNA will be extracted from peripheral blood cells of HAE patients andPCR will be performed with the flanking regions of all exons and RNA followed bysequencing. Other deletions and duplications will be analyzed by a MLPA-like technique.Protein structure and activity will be analyzed by immunoblotting and enzyme kinetics. Theresults of this project intend to clarify unknown mechanisms involving huPK activity in HAE,and can contribute to better understanding of this huPK role in other physiopathologysituations.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SERPA, FARADIBA SARQUIS; VERONEZ, CAMILA LOPES; CAMPINHOS, FERNANDA LUGAO; MOYSES, THEREZINHA RIBEIRO; PESQUERO, JOAO BOSCO. SERPING1 mutation in a rare hereditary angioedema with skin blisters. ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, v. 122, n. 3, p. 340-341, MAR 2019. (11/24142-3, 13/02661-4)

VERONEZ, CAMILA LOPES; SERPA, FARADIBA SARQUIS; PESQUERO, JOAO BOSCO. A rare mutation in the F12 gene in a patient with ACE inhibitor-induced angioedema. ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, v. 118, n. 6, p. 743-745, JUN 2017. (13/02661-4, 11/24142-3)

VERONEZ, CAMILA LOPES; MORENO, ADRIANA S.; CONSTANTINO-SILVA, ROSEMEIRE NAVICKAS; MAIA, LUANA S. M.; FERRIANI, MARIANA P. L.; CASTRO, FABIO F. M.; VALLE, SOLANGE RODRIGUES; NAKAMURA, VICTOR KOJI; CAGINI, NATHALIA; GONCALVES, ROZANA FATIMA; et al. Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, v. 6, n. 4, p. 1209+, JUL-AUG 2018. (14/27198-8, 13/02661-4, 11/24142-3, 11/23439-2)