Inhibitory immunoglobulin M antibodies to tumor necrosis factor-inducing toxins in patients with malaria.
Cytokines such as tumor necrosis factor alpha (TNF) appear to play an important role in the pathogenesis of malaria. We have previously shown that TNF is produced in response to substances released at schizont rupture, which we have called malaria toxins. In mice these toxins stimulate a T cell-independent antibody response, generating short-lived immunoglobulin M (IgM) antibodies that inhibit the TNF-inducing activity of the toxins. We report here that a similar antibody response is seen in humans. Serum from a European adult infected with Plasmodium falciparum inhibited the induction of TNF by malaria toxins derived from P. falciparum-infected erythrocytes. We found that IgM antibodies were responsible for the inhibitory activity. These inhibitory antibodies could not be detected in convalescent-phase serum collected from the same patient 6 weeks later or in sera from healthy European and African controls. The antibodies appeared to be malaria specific in that they inhibited TNF induction by a variety of P. falciparum isolates but failed to inhibit TNF induction by bacterial lipopolysaccharide or lipoteichoic acid. The inhibitory antibodies bound to liposomes containing phosphatidylinositol but not other phospholipids. Serum from a European adult infected with P. vivax also inhibited the activity of toxins derived from P. falciparum-infected erythrocytes, and this too was mediated by IgM antibodies which were malaria specific and bound to phosphatidylinositol liposomes.
Bate
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Department of Paediatrics, John Radcliffe Hospital, Oxford, United Kingdom.
Kwiatkowski
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D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008081:Liposomes / Q000378:metabolism; D008288:Malaria / Q000276:immunology*; D008297:Male; D010961:Plasmodium / Q000276:immunology / Q000472:pathogenicity*; D014118:Toxins, Biological / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000913:Antibodies, Protozoan; D007075:Immunoglobulin M; D008081:Liposomes; D014118:Toxins, Biological; D014409:Tumor Necrosis Factor-alpha