Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria

Malaria Journal

Research

Elisa Lahtela¹  Ville Holmberg²  Seppo Meri³  Päivi Onkamo⁴  Päivi Lahermo⁵  Frank P Mockenhaupt⁶  George Bedu-Addo⁷ 

[1] Department of Bacteriology and Immunology, Infection Biology Programme, Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland;Department of Bacteriology and Immunology, Infection Biology Programme, Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland;Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, P.O. Box 340, 00029 HUS, Helsinki, Finland;Department of Bacteriology and Immunology, Infection Biology Programme, Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, Helsinki, Finland;Department of Biosciences, University of Helsinki, P.O.Box 56, 00014, Helsinki, Finland;FIMM Technology Centre, University of Helsinki, P.O. Box 20, 00014, Helsinki, Finland;Institute of Tropical Medicine and International Health, Charité-University Medical Center, Spandauer Damm 130, 14050, Berlin, Germany;Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;

关键词: Lectin pathway;    Mannose-binding lectin;    MBL2;    MASP2;    Ficolin;    Complement;    Innate immunity;    Malaria;    Placenta;    Pregnancy;   

DOI  :  10.1186/1475-2875-11-61

 received in 2011-10-07, accepted in 2012-03-02,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundInnate immunity plays a crucial role in the host defense against malaria including Plasmodium falciparum malaria in pregnancy, but the roles of the various underlying genes and mechanisms predisposing to the disease are poorly understood.Methods98 single-nucletoide polymorphisms were genotyped in a set of 17 functionally related genes of the complement system in 145 primiparous Ghanaian women with placental malaria, defined by placental parasitaemia or malaria pigment, and as a control, in 124 non-affected primiparae.ResultsPlacental malaria was significantly associated with SNPs in the lectin pathway genes MBL2, MASP2, FCN2 and in properdin. In particular, the main African mannose-binding lectin deficiency variant (MBL2* G57E, rs1800451) increased the odds of placental malaria (OR 1.6; permuted p-value 0.014). In contrast, a common MASP2 mutation (R439H, rs12085877), which reduces the activity of MBL-MASP2 complexes occurred in 33% of non-affected women and in 22% primiparae with placental malaria (OR 0.55, permuted p-value 0.020).ConclusionsExcessive complement activation is of importance in the pathogenesis of placental malaria by mediating inflammation, coagulation, and endothelial dysfunction. Mutated MBL and MASP2 proteins could have direct intrinsic effects on the susceptibility to placental malaria, in addition to their roles in regulation of downstream complement activation.

【 授权许可】

CC BY   
© Holmberg et al; licensee BioMed Central Ltd. 2012