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Relevance of Fcgamma receptor and interleukin-10 polymorphisms for meningococcal disease
W L van der Pol1, T W Huizinga, G Vidarsson
1University Medical Center, Dept. of Immunology, Laboratory for Immunotherapy, 3584 EA Utrecht, The Netherlands. L.vdPol@lab.azu.nl
Abstract:
The contribution of individual Fcgamma receptor (FcgammaR) subclasses to meningococcal phagocytosis was studied. In addition, functional FcgammaR polymorphisms were determined in 50 patients with meningococcal disease (MD), in 183 first-degree relatives of MD patients, and in 239 healthy control subjects, to study the association of FcgammaR genotypes with disease. Efficient internalization of opsonized Neisseria meningitidis serogroup B was mediated via multiple FcgammaR subclasses on phagocytes. Accordingly, a low-efficiency combination of FcgammaRIIa-R/R131, FcgammaRIIIa-F/F158, and FcgammaRIIIb-NA2/2 genotypes was increased significantly in relatives of patients with MD, compared with healthy control subjects (P<.05; odds ratio, 2.6; 95% confidence interval, 1.1-6.3). FcgammaRIIa and FcgammaRIIIa genotype distributions differed between patients with sepsis and those with meningitis. Combined genotypes of FcgammaRIIa and interleukin-10 -1082, which was previously reported as being associated with MD outcome, were distributed randomly in control subjects but not in relatives of patients with MD (P<.01). These data provide further evidence for the association of polymorphic genes on chromosome 1 and MD.
Insights
Fcgamma receptors (FcgammaR) play a role in fighting meningococcal disease. Specific FcgammaR genotypes are associated with increased risk in families of patients with meningococcal disease.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Neisseria meningitidis causes meningococcal disease (MD).
- Fcgamma receptors (FcgammaR) mediate phagocytosis of bacteria.
- FcgammaR polymorphisms may influence susceptibility to MD.
Purpose of the Study:
- To investigate the role of FcgammaR subclasses in meningococcal phagocytosis.
- To determine the association between FcgammaR genotypes and MD.
- To explore FcgammaR genotype associations in patients, relatives, and controls.
Main Methods:
- Studied FcgammaR contribution to phagocytosis of Neisseria meningitidis serogroup B.
- Genotyped FcgammaR polymorphisms in 50 MD patients, 183 relatives, and 239 controls.
- Analyzed combined genotypes with interleukin-10 -1082.
Main Results:
- Multiple FcgammaR subclasses efficiently mediate opsonized meningococcal internalization.
- A low-efficiency FcgammaR genotype combination was significantly increased in MD relatives.
- FcgammaR genotype distributions differed between sepsis and meningitis patients.
- Combined FcgammaRIIa and IL-10 genotypes showed significant association in MD relatives.
Conclusions:
- Fcgamma receptors are crucial for clearing meningococcal infections.
- Specific FcgammaR genotypes are associated with increased risk and outcome in meningococcal disease.
- Polymorphic genes on chromosome 1 are linked to meningococcal disease susceptibility.