Fc gamma RIIa (CD32): A potential marker defining susceptibility to localized juvenile periodontitis

EPIDEMIOLOGIC STUDIES INDICATE THAT BLACKS are at greater risk for development of localized juvenile periodontitis (LJP) than other ethnic groups. It has also been observed that, despite the relatively uncommon nature of this form of early-onset periodontitis, LJP often tends to cluster within families, which suggests that susceptibility to this disease may be inherited. Immunologic studies of a predominantly black population of LJP subjects have revealed that many of these patients mount a strong IgG response to Actinobacillus actinomycetemcomitans. A substantial proportion of this response is comprised of antibodies of the IgG2 subclass. IgG antibodies are required for efficient phagocytosis and killing of A. actinomycetemcomitans by human neutrophils. Recognition of bacteria coated with IgG antibodies is a process which is mediated by IgG Fc receptors (Fc gamma R) expressed on mononuclear and polymorphonuclear phagocytes. A major class of Fc gamma R found on neutrophils is a transmembrane receptor (Fc gamma RII, or CD32) which binds IgG with low affinity. Recently, a genetically determined biallelic polymorphism has been described for this receptor. One allotype, termed H131, binds human IgG2 efficiently, whereas the alternative form, R131, does not. Neutrophils expressing the H131 allotype of Fc gamma RII readily ingest and destroy IgG2-coated A. actinomycetemcomitans, whereas neutrophils bearing the R131 allotype do not. We hypothesize that the increased risk among blacks for development of LJP may be due to a combination of two factors, which include: 1) a tendency toward preferential synthesis of IgG2 antibodies to A. actinomycetemcomitans; and 2) an increased frequency of the R131 allele of Fc gamma RIIa in this subject population.