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

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概要

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• 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 P. falciparum and P. vivax are prevalent. We determined P. falciparum/ P. vivax 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.

• 日本熱帯医学会,The Japanese Society of Tropical Medicineの論文
• 2008-06-01

著者

• HIRAYAMA Kenji

  Department of Physics, Chiba University

• KOBAYAKAWA Takatoshi

  Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University

• Kikuchi Mihoko

  Department Of Immunogenetics Institute Of Tropical Medicine (nekken) Nagasaki University

• Hirayama Kenji

  Department Of Immunogenetics Institute Of Tropical Medicine (nekken) Nagasaki University

• Hirayama Kenji

  Department Of Clinical Immunology Medical Institute Of Bioregulation Kyushu University

• Tsukahara Takahiro

  Department Of International Affairs And Tropical Medicine Tokyo's Women's Medical Universi

• KANEKO Akira

  Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University

• OSAWA HIKOTA

  Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University

• TROYE-BLOMBERG Marita

  Department of Immunology, Stockholm University

• HOMBHANJE Francis

  School of Medicine and Health Sciences, University of Papua New Guinea

• TANIHATA Takeo

  Malaria Research Laboratory, Department of Medicine, Karolinska Institutet

• UDOMSANGPETCH Rachanee

  Department of Pathobiology, Faculty of Science, Mahidol University

• BJORKMAN Anders

  Malaria Research Laboratory, Department of Medicine, Karolinska Institutet

• Blomberg Marita

  Department Of Immunology Stockholm University

• Troye-blomberg Marita

  Department Of Immunology Stockholm University Stockholm Sweden

• Kobayakawa Takatoshi

  Department Of International Affairs And Tropical Medicine Tokyo Women's Medical University

• Osawa Hikota

  Department Of International Affairs And Tropical Medicine Tokyo Women's Medical University

• Kaneko Akira

  Malaria Research Unit Unit For Infectious Disease Department Of Medicine Karolinska University Hospi

• Hombhanje Francis

  School Of Medicine And Health Sciences University Of Papua New Guinea

• Bjorkman Anders

  Malaria Research Laboratory Department Of Medicine Karolinska Institutet

• Kaneko Akira

  Department Of Gastroenterology And Hepatology Osaka University Graduate School Of Medicine

• Udomsangpetch Rachanee

  Department Of Pathobiology Faculty Of Science Mahidol University

• Kaneko Akira

  Department Of Agricultrural Chemistry And Department Of Forestry Faculty Of Agriculture Ehime Univer

• Bj?rkman Anders

  Malaria Research Laboratory, Department of Medicine, Karolinska Institutet

• KIKUCHI Mihoko

  Department of Immunogenetics and Global Centre of Excellence, Institute of Tropical Medicine, Nagasaki University

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