IgE and tumor necrosis factor in malaria infection

IgE, the immunoglobulin instrumental in atopic diseases is also elevated in many infections. This paper reports on the occurrence and possible pathoge nic role of IgE in human Plasmodium falciparum malaria, one of the most wid ely spread and severe infectious diseases world wide. Plasmodial infections induce IgE elevation in the blood of the majority of people living in mala ria endemic areas and up to 5% of this TEE constitutes anti-malaria antibod ies. Production of IgE is controlled by T cells and elevated IgE concentrat ions 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 mo nozygotic or dizygotic twins originating from malarious areas of Africa. Wh ile these levels were indistinguishable within monozygotic twin pairs, they were different within the dizygotic pairs. Comparison of the levels of tot al IgE or IgE anti-malaria antibodies in patients with uncomplicated malari a with those in patients with the severe form of the disease (cerebral mala ria or severe malaria without cerebral involvement) indicate that these lev els 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 c ause TNF release from monocytes in a reaction dependent on the presence of IgE containing immune complexes or aggregates. This results in induction an d cross-linking of Fc(epsilon) receptor II (CD23) and by binding to and act ivating 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. (C) 1999 Els evier Science B.V. All rights reserved.