CTLA-4 polymorphisms and anti-malarial antibodies in a hyper-endemic population of Papua New Guinea

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Author(s)

    • OSAWA Hikota
    • Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University
    • HIRAYAMA Kenji
    • Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University
    • KIKUCHI Mihoko
    • Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University
    • TANIHATA Takeo
    • Malaria Research Laboratory, Department of Medicine, Karolinska Institutet
    • BJORKMAN Anders
    • Malaria Research Laboratory, Department of Medicine, Karolinska Institutet
    • KOBAYAKAWA Takatoshi
    • Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University
    • KANEKO Akira
    • Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University

Abstract

In malaria endemic areas, people naturally acquire an age-related immunity to malaria. Part of this immunity involves anti-malarial specific antibodies. Acquisition of these malaria-specific antibodies depends not only on exposure to malaria parasites but also on the human genetic predisposition. CTLA-4 is a costimulatory molecule that delivers an inhibitory signal to suppress T-cell as well as B-cell responses. We investigated associations between malaria-specific antibody levels and CTLA-4 polymorphisms in 189 subjects living in a hyper-endemic area of Papua New Guinea (PNG), where both <I>P. falciparum</I> and <I>P. vivax</I> are prevalent. We determined <I>P. falciparum⁄ P. vivax</I> specific IgG⁄IgE levels (Pf-IgG, Pv-IgG, Pf-IgE, Pv-IgE) and polymorphisms in the CTLA-4 gene at position -1661 promoter region (A⁄G), the +49 exon 1 non-synonymous mutation (A⁄G), and the +6230 3‘-UTR (A⁄G). All quantified antibody levels were significantly higher in subjects > 5 years (n = 150) than in subjects ≤ 5 years of age (n = 39). In children ≤ 5 years old, significant associations were detected between CTLA-4 +49 (GG⁄AG vs. AA) and Pv-IgG (median 18.7 vs. 13.7 Μg⁄ml, P = 0.017) and Pv-IgE (266.6 vs. 146.5 pg⁄ml, P = 0.046). No significant difference was observed in subjects > 5 years old. These results suggest that the CTLA-4+49 polymorphism influenced Pv-IgG and Pv-IgE levels among children less than five years old in the studied population, which may regulate the age- and species-specific clinical outcomes of malaria infection.

Journal

  • Tropical Medicine and Health

    Tropical Medicine and Health 36(2), 93-100, 2008-06-01

    The Japanese Society of Tropical Medicine

References:  43

Codes

  • NII Article ID (NAID)
    10024175082
  • NII NACSIS-CAT ID (NCID)
    AA11912846
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    13488945
  • Data Source
    CJP  IR  J-STAGE 
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