Association of FcgammaR and CR3 polymorphisms with bacterial infections in systemic lupus erythematosus: determination of the genotype combinations and their influence on the neutrophil effector functions

• Grant number: 09/14732-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2010
• End date: January 31, 2012
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Cleni Mara Marzocchi Machado
• Grantee: Cleni Mara Marzocchi Machado
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Infections represent 20-55% of all deaths in patients with systemic lupus erythematosus (SLE). About 80% of them are caused by bacteria. SLE is an autoimmune disease in which disease-related and genetic factors and immunosuppressive and cytotoxic therapies all contribute to an increased susceptibility to infections. Factors predisposing to infection include defects in chemotaxis, abnormalities in neutrophil phagocytic activity, decreased immune complex and bacteria clearance, neutropenia, reduced oxidative burst, abnormalities in the expression of Fcgamma (FcgR) and complement (CR) receptors. Recent data have provided evidence that genetic polymorphism of FcgR is associated with immune abnormalities and risk to development of SLE. FcgR can mediate neutrophil effector functions and play a synergistic action with CR. FcgRIIa and FcgRIIIb display functionally relevant genetic polymorphisms, which allelic variants can influence the biological responses and the susceptibility to and course of infectious diseases. In particular, the presence of the FcgRIIa-R131 allotype results in lower affinity binding to IgG2, a subclass of IgG specific for encapsulated bacteria. Since Pneumococcus accounts for 6-18% of all bacterial infections in SLE, the R131 allele can be relevant as a risk factor for infections.The aim of this study is to investigate the influence of the FcgR polymorphisms on the oxidative burst, phagocytosis and degranulation of neutrophils, associated with CR3 polymorphism, and bacterial infections in SLE. This study can contribute for the understanding of neutrophil abnormalities in SLE and identifying genetic markers that would predict patients who are at high risk for infections. (AU)

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)

COSTA VIGATO-FERREIRA, ISABEL CRISTINA; TOLLER-KAWAHISA, JULIANA ESCHER; TRES PANCOTO, JOAO ALEXANDRE; MENDES-JUNIOR, CELSO TEIXEIRA; MARTINEZ, EDSON ZANGIACOMI; DONADI, EDUARDO ANTONIO; LOUZADA-JUNIOR, PAULO; CAVALCANTI DEL LAMA, JOSE EDUARDO; MARZOCCHI-MACHADO, CLENI MARA. Fc gamma RIIa and Fc gamma RIIIb polymorphisms and associations with clinical manifestations in systemic lupus erythematosus patients. AUTOIMMUNITY, v. 47, n. 7, p. 451-458, NOV 2014. (09/12649-6, 09/14732-8)

TOLLER-KAWAHISA, JULIANA ESCHER; COSTA VIGATO-FERREIRA, ISABEL CRISTINA; TRES PANCOTO, JOAO ALEXANDRE; MENDES-JUNIOR, CELSO TEIXEIRA; MARTINEZ, EDSON ZANGIACOMI; PALOMINO, GUSTAVO MARTELLI; LOUZADA-JUNIOR, PAULO; DONADI, EDUARDO ANTONIO; CAVALCANTI DEL LAMA, JOSE EDUARDO; MARZOCCHI-MACHADO, CLENI MARA. The variant of CD11b, rs1143679 within ITGAM, is associated with systemic lupus erythematosus and clinical manifestations in Brazilian patients. HUMAN IMMUNOLOGY, v. 75, n. 2, p. 119-123, FEB 2014. (09/12649-6, 09/14732-8)