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Meningococcal disease and polymorphism of FcgammaRIIa (CD32) in late complement component-deficient individuals
A E Platonov1, E J Kuijper, I V Vershinina
1Central Institute of Epidemiology, Moscow, Russia.
Abstract:
Late complement component-deficient (LCCD) individuals lack plasma bactericidal activity and are highly susceptible to meningococcal disease. Phagocytosis plays a significant role in immune defence against meningococci and involves FcgammaRIIa (CD32) on leucocytes. Two allotypic forms are currently recognized: FcgammaRIIa-R131 and RIIa-H131. Neutrophils with the IIa-H/H131 allotype are more effective in phagocytosis than IIa-R/R131. We studied the distributions of IIa-R131 and IIa-H131 allotypes among 29 Russian LCCD patients who had suffered from recurrent episodes of meningococcal disease. The distribution of IIa-R/R131 to heterozygous IIa-R/H131 to homozygous IIa-H/H131 genotypes was 0.14:0.29:0.57 for LCCD patients who developed the first episode of disease before 10 years of age. The distribution was 0.21:0.64:0.14 for patients who experienced meningococcal disease above the age of 10 years (chi2 = 6, P < 0.05, odds ratio for IIa H/H131 versus R/R131 = 8). Meningococcal disease had a 'grave' course in 14 of 31 disease episodes in patients with IIa-R/R131 and IIa-R/H131 allotypes, in contrast to 1 of 18 episodes in patients with IIa-H/H131 allotype (chi2 = 7, P < 0.01, odds ratio = 14). We conclude that IIa-H/H131 individuals appear to have a higher acquired antibody-mediated phagocytosis-dependent resistance to meningococcal disease above the age of 10 years. Additionally, effective CD32-mediated phagocytosis may restrict the severity of meningococcal disease in LCCD patients with IIa-H/H131 phenotype.
Insights
Individuals with the FcgammaRIIa-H/H131 allotype show increased resistance to meningococcal disease, particularly after age 10. This FcgammaRIIa (CD32) phenotype enhances antibody-mediated phagocytosis, reducing disease severity in complement-deficient patients.
Area of Science:
- Immunology
- Genetics
Background:
- Late complement component-deficient (LCCD) individuals are highly susceptible to meningococcal disease due to impaired plasma bactericidal activity.
- FcgammaRIIa (CD32) mediated phagocytosis is crucial for defense against Neisseria meningitidis.
- Two FcgammaRIIa allotypes, R131 and H131, exist, with H131 neutrophils showing more effective phagocytosis.
Purpose of the Study:
- To investigate the distribution of FcgammaRIIa (CD32) allotypes in Russian LCCD patients with recurrent meningococcal disease.
- To determine if FcgammaRIIa allotypes influence susceptibility and disease severity in LCCD patients.
Main Methods:
- Genotyping of FcgammaRIIa-R131 and FcgammaRIIa-H131 allotypes in 29 LCCD patients.
- Analysis of allotype distribution based on age of first meningococcal disease episode.
- Comparison of disease severity (grave course) between different FcgammaRIIa allotypes.
Main Results:
- The distribution of FcgammaRIIa genotypes differed significantly between LCCD patients with early (<10 years) and later (≥10 years) onset of meningococcal disease.
- Patients with the FcgammaRIIa-H/H131 genotype had a significantly lower risk of severe meningococcal disease compared to those with R/R131 or R/H131 allotypes (OR=14).
- The FcgammaRIIa-H/H131 allotype was associated with a higher frequency in patients experiencing meningococcal disease after age 10.
Conclusions:
- The FcgammaRIIa-H/H131 allotype is associated with enhanced antibody-mediated phagocytosis-dependent resistance to meningococcal disease in LCCD individuals, particularly after age 10.
- Effective CD32-mediated phagocytosis conferred by the IIa-H/H131 phenotype may limit meningococcal disease severity in LCCD patients.