IgE and tumor necrosis factor in malaria infection

Abstract

IgE, the immunoglobulin instrumental in atopic diseases is also elevated in many infections. This paper reports on the occurrence and possible pathogenic role of IgE in human Plasmodium falciparum malaria, one of the most widely spread and severe infectious diseases world wide. Plasmodial infections induce IgE elevation in the blood of the majority of people living in malaria endemic areas and up to 5% of this IgE constitutes anti-malaria antibodies. Production of IgE is controlled by T cells and elevated IgE concentrations in the blood of malaria patients are the result of an increased ratio of T-helper 2 (Th2) over T-helper 1 (Th1) cells. The underlying Th1 to Th2 switch is controlled by a variety of environmental and genetic factors. The importance of the latter is demonstrated by the IgE levels occurring in monozygotic or dizygotic twins originating from malarious areas of Africa. While these levels were indistinguishable within monozygotic twin pairs, they were different within the dizygotic pairs. Comparison of the levels of total IgE or IgE anti-malaria antibodies in patients with uncomplicated malaria with those in patients with the severe form of the disease (cerebral malaria or severe malaria without cerebral involvement) indicate that these levels are significantly higher in the cases with severe disease. This is the reverse with IgG and suggests that IgE plays a role in malaria pathogenesis. An important pathogenic mediator causing malaria fever and tissue lesions is tumor necrosis factor (TNF), generally believed to be induced by toxins released from the parasite. However, sera from malaria patients can also cause TNF release from monocytes in a reaction dependent on the presence of IgE containing immune complexes or aggregates. This results in induction and cross-linking of Fcepsilon receptor II (CD23) and by binding to and activating these cells, IgE will contribute to a local over-production of TNF in capillaries and post-capillary venules where P. falciparum parasites or their products accumulate in the severe forms of this disease.