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Molecular genetic mechanisms of primary immunodeficiencies

Abstract

Primary immunodeficiencies are a group of approximately 300 diseases that may present with increased susceptibility to infections, autoimmunity, inflammation, allergies, and increased susceptibility to Cancer. In the present proposal, we will investigate chronic granulomatous disease (CGD), X-linked Hyper IgM Syndrome (X-HIGM), and Severe Combined Immunodeficiency (SCID). As well, we will introduce a new and current topic for investigation: are there genetic factors predisposing to Zika Virus infections and its complications? We will continue our investigation about the immunopathology and susceptibility to infections, mainly mycobacteria, in CGD. We will analyze neutrophils, macrophages, and dendritic cells from these patients, searching for hyperinflammation markers predisposing to tissue damage and greater susceptibility to infections. On the other hand, we will continue our investigation about X-HIGM, analyzing the effect of interferon gamma on the functional defects of dendritic cells and neutrophils from these patients, hoping to identify the basis for alternative therapies for these patients. As well, we will investigate the molecular genetic factors of SICD in our region, as we continue our program on newborn screening for this disease. Finally, we will investigate possible genetic markers predisposing to Zika Virus infection and its complications, mainly microcephaly, trying to open new avenues for therapeutic and prophylactic interventions in this current world endemic. (AU)

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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)
FRANCA, TABATA TAKAHASHI; AL-SBIEI, ASHRAF; BASHIR, GHADA; MOHAMED, YASSIR AWAD; SALGADO, RANIERI COELHO; BARREIROS, LUCILA AKUNE; DA SILVA NAPOLEAO, SARAH MARIA; WEBER, CRISTINA WORM; SEVERO FERREIRA, JANAIRA FERNANDES; ARANDA, CAROLINA SANCHEZ; PRANDO, CAROLINA; DE BARROS DORNA, MAYRA B.; JURISICA, IGOR; FERNANDEZ-CABEZUDO, MARIA J.; OCHS, HANS D.; CONDINO-NETO, ANTONIO; AL-RAMADI, BASEL K.; CABRAL-MARQUES, OTAVIO. CD40L modulates transcriptional signatures of neutrophils in the bone marrow associated with development and trafficking. JCI INSIGHT, v. 6, n. 16 AUG 23 2021. Web of Science Citations: 0.
FRANCA, TABATA T.; BARREIROS, LUCILA A.; AL-RAMADI, BASEL K.; OCHS, HANS D.; CABRAL-MARQUES, OTAVIO; CONDINO-NETO, ANTONIO. CD40 ligand deficiency: treatment strategies and novel therapeutic perspectives. EXPERT REVIEW OF CLINICAL IMMUNOLOGY, v. 15, n. 5, p. 529-540, MAY 4 2019. Web of Science Citations: 2.
CABRAL-MARQUES, OTAVIO; FRANCA, TABATA TAKAHASHI; AL-SBIEI, ASHRAF; SCHIMKE, LENA FRIEDERIKE; KHAN, TAJ ALI; FERIOTTI, CLAUDIA; DA COSTA, TANIA ALVES; REIS JUNIOR, OSVALDO; WEBER, CRISTINA WORM; FERREIRA, JANAIRA FERNANDES; TAVARES, FABIOLA SCANCETTI; VALENTE, CLAUDIA; WATANABE DI GESU, REGINA SUMIKO; LQBAL, ASIF; RIEMEKASTEN, GABRIELA; AMARANTE-MENDES, GUSTAVO PESSINI; MARZAGIO BARBUTO, JOSE ALEXANDRE; COSTA-CARVALHO, BEATRIZ TAVARES; SOEIRO PEREIRA, PAULO VITOR; FERNANDEZ-CABEZUDO, MARIA J.; GARCIA CALICH, VERA LUCIA; NOTARANGELO, LUIGI D.; TORGERSON, TROY R.; AL-RAMADI, BASEL K.; OCHS, HANS D.; CONDINO-NETO, ANTONIO. CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-gamma. Journal of Allergy and Clinical Immunology, v. 142, n. 5, p. 1571+, NOV 2018. Web of Science Citations: 5.

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