Human Fc gamma RIIa has 2 codominantly expressed allotypes, which differ gr
eatly in their ability to ligate immunoglobulin G(2) (IgG(2)). Whereas Fc g
amma RIIa-R131 binds only weakly to IgG(2), Fc gamma RIIa-H131 binds to it
efficiently and might be primarily responsible for the phagocytosis of IgG(
2)-opsonized bacteria. IgG(2) plays a pivotal role in defense against pneum
ococcal infection. This prospective study showed that 50% of patients with
bacteremic pneumococcal pneumonia were homozygous for Fc gamma RIIa-R131, c
ompared with 28% with nonbacteremic pneumococcal pneumonia and 29% of uninf
ected controls (P < .05). The gene frequency of Fc gamma RIIa-R131 was 0.67
in bacteremic patients, significantly higher than in the other groups (P <
.05), All bacteremic patients who died within 1 week of hospitalization we
re homozygous for Fc gamma RIIa-R131. Therefore, the severity of pneumococc
al infection may, in part, be genetically mediated. Taken together with sim
ilar findings in cases of meningococcal disease, these results suggest that
such genetic factors may be generalizable to infections caused by encapsul
ated bacteria.