RGD Reference Report - The role of Fcgamma receptor polymorphisms and C3 in the immune defence against Neisseria meningitidis in complement-deficient individuals. - Rat Genome Database

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The role of Fcgamma receptor polymorphisms and C3 in the immune defence against Neisseria meningitidis in complement-deficient individuals.

Authors: Fijen, CA  Bredius, RG  Kuijper, EJ  Out, TA  De Haas, M  De Wit, AP  Daha, MR  De Winkel, JG 
Citation: Fijen CA, etal., Clin Exp Immunol. 2000 May;120(2):338-45.
RGD ID: 5147980
Pubmed: PMID:10792385   (View Abstract at PubMed)
PMCID: PMC1905639   (View Article at PubMed Central)

Individuals with either a late (C5-9) complement component deficiency (LCCD) or properdin deficiency are at increased risk to develop meningococcal disease, often due to serogroups W135 and Y. Anti-meningococcal defence in both LCCD persons and properdin-deficient individuals without bactericidal antibodies depends mainly on phagocytosis. Three types of opsonin receptors are involved in phagocytosis by polymorphonuclear cells (PMN). These represent the polymorphic FcgammaRIIa (CD32) and FcgammaRIIIb (CD16b) receptors, and the C3 receptor CR3 (CD11b/CD18). When the distribution of FcgammaRIIa and FcgammaRIIIb allotypes was assessed in 15 LCCD and in 15 properdin-deficient patients with/without previous meningococcal disease, we found the combination of FcgammaRIIa-R/R131 with FcgammaRIIIb-NA2/NA2 allotypes to be associated with previous meningococcal disease (odds ratio 13.9, Fisher's test P = 0.036). No such relation was observed in the properdin-deficient patients. The importance of FcgammaRIIa allotypes was also demonstrated using in vitro phagocytosis assays. PMN from FcgammaRIIa-R/R131 homozygous donors internalized IgG2 opsonized meningococci W135 significantly (P < 0.05) less than PMN from FcgammaRIIa-H/H131 donors. When properdin-deficient serum was tested, it was observed that reconstitution with properdin resulted in enhanced PMN phagocytosis of the W135 meningococci (P = 0.001). This enhanced phagocytosis was parallelled by an increase in C3 deposition onto the opsonized meningococci W135 (r = 0.6568, P = 0. 01). We conclude that the occurrence of meningococcal disease in LCCD patients is associated with certain FcgammaR allotypes. Properdin-deficient individuals are susceptible to meningococcal disease because of an insufficient C3 deposition on the surface of meningococci, resulting in insufficient phagocytosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumanMeningococcal Infections  IAGP associated with complement deficiency and DNA:missense mutation:cds:p.H131R (human)RGD 
Fcgr2aRatMeningococcal Infections  ISOFCGR2A (Homo sapiens)associated with complement deficiency and DNA:missense mutation:cds:p.H131R (human)RGD 
Fcgr3MouseMeningococcal Infections  ISOFCGR2A (Homo sapiens)associated with complement deficiency and DNA:missense mutation:cds:p.H131R (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR2AHumanOpportunistic bacterial infection susceptibilityIAGP associated with complement deficiency and DNA:missense mutation:cds:p.H131RRGD 
Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)


Additional Information