The role of Fcγreceptor polymorphisms and C3 in the immune defence againstNeisseria meningitidisin complement-deficient individuals

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Abstract
SUMMARY: 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 FcγRIIa (CD32) and FcγRIIIb (CD16b) receptors, and the C3 receptor CR3 (CD11b/CD18). When the distribution of FcγRIIa and FcγRIIIb allotypes was assessed in 15 LCCD and in 15 properdin-deficient patients with/without previous meningococcal disease, we found the combination of FcγRIIa-R/R131 with FcγRIIIb-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 FcγRIIa allotypes was also demonstrated using in vitro phagocytosis assays. PMN from FcγRIIa-R/R131 homozygous donors internalized IgG2 opsonized meningococci W135 significantly (P < 0·05) less than PMN from FcγRIIa-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 FcγR allotypes. Properdin-deficient individuals are susceptible to meningococcal disease because of an insufficient C3 deposition on the surface of meningococci, resulting in insufficient phagocytosis.