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Increased Human IgE Induced by Killing Schistosoma mansoni In Vivo Is Associated with Pretreatment Th2 Cytokine Responsiveness to Worm Antigens¹

Klaudia Walter^2,*, Anthony J. C. Fulford^3,*, Rowena McBeath^*, Sarah Joseph^4,*, Frances M. Jones^*, H. Curtis Kariuki, Joseph K. Mwatha, Gachuhi Kimani, Narcis B. Kabatereine, Birgitte J. Vennervald^¶, John H. Ouma^5, and David W. Dunne^*

^* Division of Microbiology and Parasitology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom; Division of Vector Borne Diseases, Ministry of Health, Nairobi, Kenya; Kenyan Medical Research Institute, Ministry of Health, Nairobi, Kenya; Vector Control Division, Ministry of Health, Kampala, Uganda; and ^¶ DBL-Institute for Health, Research and Development, Charlottenlund, Denmark

In schistosomiasis endemic areas, children are very susceptible to postchemotherapy reinfection, whereas adults are relatively resistant. Different studies have reported that schistosome-specific IL-4 and IL-5 responses, or posttreatment worm-IgE levels, correlate with subsequent low reinfection. Chemotherapy kills i.v. worms providing an in vivo Ag challenge. We measured anti-worm (soluble worm Ag (SWA) and recombinant tegumental Ag (rSm22.6)) and anti-egg (soluble egg Ag) Ab levels in 177 Ugandans (aged 7–50) in a high Schistosoma mansoni transmission area, both before and 7 wk posttreatment, and analyzed these data in relation to whole blood in vitro cytokine responses at the same time points. Soluble egg Ag-Ig levels were unaffected by treatment but worm-IgG1 and -IgG4 increased, whereas worm-IgE increased in many but not all individuals. An increase in worm-IgE was mainly seen in >15-year-olds and, unlike in children, was inversely correlated to pretreatment infection intensities, suggesting this response was associated both with resistance to pretreatment infection, as well as posttreatment reinfection. The increases in SWA-IgE and rSm22.6-IgE positively correlated with pretreatment Th2 cytokines, but not IFN-, induced by SWA. These relationships remained significant after allowing for the confounding effects of pretreatment infection intensity, age, and pretreatment IgE levels, indicating a link between SWA-specific Th2 cytokine responsiveness and subsequent increases in worm-IgE. An exceptionally strong relationship between IL-5 and posttreatment worm-IgE levels in <15-year-olds suggested that the failure of younger children to respond to in vivo Ag stimulation with increased levels of IgE, is related to their lack of pretreatment SWA Th2 cytokine responsiveness.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This project was funded by the Wellcome Trust, the Medical Research Council, and the Commission of the European Community’s Science and Technology for Development Programme (INCO-DC Contract IC18-CT97-0237 and INCO-DEV Contract ICA4-CT1999-10003).

² Address correspondence and reprint requests to Klaudia Walter, Medical Research Council Biostatistics Unit, Institute of Public Health, University of Cambridge, University Forvie Site, Robinson Way, Cambridge CB2 2SR, U.K. E-mail address: klaudia.walter{at}mrc-bsu.cam.ac.uk

³ Current address: Medical Research Council International Nutrition Group, Nutrition and Public Health Interventions Research Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, U.K.

⁴ Current address: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa.

⁵ Current address: Maseno University, Kisumu/Busia Road, Private Bag, Maseno, Kenya.

⁶ Abbreviations used in this paper: PZQ, praziquantel; SEA, soluble egg Ag; SWA, soluble worm Ag; epg, eggs per gram; CI_95%, 95% confidence interval.

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