IGHG3 G and the pathogenesis of hyperreactive malarious splenomegaly.

Hyperreactive malarious splenomegaly is an aberrant response to chronic malarial infection, defined by persistent gross splenomegaly and elevated serum IgM and IgG. The populational and familial patterns of this disorder suggest genetically based, immune incompetence. In Papua New Guinea, the disease occurs among populations characterized by high frequencies of IGHG3 G haplotypes. Elsewhere, the distribution and prevalence of hyperreactive malarious splenomegaly is consistent with the distributions of IGHG3 alleles. Drawing upon this relationship, I suggest that expression of the G3M G phenotype is a necessary precondition for hyperreactive malarious splenomegaly, consistent with the pathogenesis of malaria and the functions of the immune system.