Fc?R e CR3 no lúpus eritematoso sistêmico: variantes polimórficas e sua influência na fagocitose e desgranulação dos neutrófilos / Fc?R and CR in systemic lupus erythematosus: polimorphisms and their influence in the phagocytosis and degranulation of neutrophils

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

02/08/2012

RESUMO

Systemic lupus erythematosus (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 (IC) and bacteria clearance, neutropenia, reduced oxidative burst, abnormalities in the expression of Fc?R (Fc?R) and complement (CR) receptors. Recent data have provided evidence that genetic polymorphism of Fc?R is associated with immune abnormalities and risk to development of SLE. Fc?R can mediate neutrophil effector functions and play a synergistic action with CR. Fc?RIIa and Fc?RIIIb 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 Fc?RIIa-R131 allotype results in lower affinity binding to IgG2, a subclass of IgG specific for encapsulated bacteria. Since pneumococci 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 was to investigate the influence of the Fc?R polymorphisms on the phagocytosis and degranulation of neutrophils, associated with CR3 polymorphism, and bacterial infections in SLE. Genotypes were determined by polymerase chain reactions for the polymorphisms of the allelic variants; the phagocytosis and the degranulation were stimulated with IC-containing IgG (IC-IgG) and IC-IgG and complement (IC-IgG/NHS); the phagocytosis of IC by neutrophils and expression of Fc?R and CR3 were evaluated by flow cytometry, and degranulation of neutrophils stimulated with IC was measured by the release of lysozyme and elastase. The results showed a higher frequency for the genotype R-131 in SLE and association of genotype HNA-4a negative for the CR3 with susceptibility to SLE and association of HNA-4a with protection; the phagocytosis was lower in neutrophils from patients with SLE with HR-131 genotype than those in neutrophils from control group with genotype R-131 (IC-IgG and IC-IgG/NHS); in the Fc?RIIIb polymorphism, the phagocytosis and lysozyme were lower in neutrophils from patients with SLE with genotype HNA-1b and higher for HNA-1a/1b than those controls with the respective genotypes (IC-IgG/NHS); the occurrence of infections was more frequently associated with the presence of the allele R-131 and HNA-1b; no difference was observed for polymorphism HNA-4a of the CR3, neither for elastase. 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.

ASSUNTO(S)

complement degranulation desgranulação fagocitose fcgamma recepto lúpus eritematoso sistêmico neutrófilos neutrophils phagocytosis polimorfismos receptor para complemento receptores para igg systemic lupus erythematosus

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