IMMUNOGLOBULIN-E, A PATHOGENIC FACTOR IN PLASMODIUM-FALCIPARUM MALARIA

Most children and adults living in areas where the endemicity of Plasm odium falciparum is high have significantly elevated levels of both to tal immunoglobulin E (IgE) and IgE antimalarial antibodies in blood. T his elevation is highest in patients Kith cerebral malaria, suggesting a pathogenic role for this immunoglobulin isotype. In this study, we show that IgE elevation map also be seen in severe malaria without cer ebral involvement and parallels an elevation of tumor necrosis factor alpha (TNF), IgE-containing serum from malaria immune donors was added to tissue culture plates coated with rabbit anti-hum an IgE antibodie s or with P. falciparum antigen, IgE-anti-IgE complexes as well as ant igen-binding IgE antibodies induced TNF release from peripheral blood mononuclear cells (PBMC). Nonmalaria control sera with no IgE elevatio n induced significantly less of this cytokine. and the TNF-inducing ca pacity of malaria sera was also strongly reduced by passing them over anti-IgE Sepharose columns. The cells giving rise to TNF were adherent PBMC. The release of this cytokine probably reflects cross-linking of their low-affinity receptors for IgE (CD13) by IgE-containing immune complexes known to give rise to monocyte activation,ia the NO transduc tion pathway. In line with this, adherent monocytic cells exposed to I gE complexes displayed increased expression of CD23, As the malaria se ra contained Ige anti-IgE antibodies, such complexes probably also pla y a role in the induction of TNF; in vivo, Overproduction of TNF is co nsidered a major pathogenic mechanism responsible for fever and tissue lesions in P. falciparum malaria. This overproduction is generally as sumed to reflect a direct stimulation of effector cells by certain par asite-derived toxins. Our results suggest that IgE elevation constitut es yet another important mechanism involved in excessive TNF induction ill this disease.