IGHG3-G AND THE PATHOGENESIS OF HYPERREACTIVE MALARIOUS SPLENOMEGALY

Hyperreactive malarious splenomegaly is an aberrant response to chroni c malarial infection, defined by persistent gross splenomegaly and ele vated serum IgM and IgG. The populational and familial patterns of thi s disorder suggest genetically based, immune incompetence. In Papua Ne w Guinea, the disease occurs among populations characterized by high f requencies of IGHG3 G haplotypes. Elsewhere, the distribution and prev alence of hyperreactive malarious splenomegaly is consistent with the distributions of IGHG3 alleles. Drawing upon this relationship, I sugg est that expression of the G3M G phenotype is a necessary precondition for hyperreactive malarious splenomegaly, consistent with the pathoge nesis of malaria and the functions of the immune system.