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Chitinase 3-like 1 is induced by Plasmodium falciparum malaria and predicts outcome of cerebral malaria and severe malarial anaemia in a case-control study of African children.
- Source :
-
Malaria journal [Malar J] 2014 Jul 21; Vol. 13, pp. 279. Date of Electronic Publication: 2014 Jul 21. - Publication Year :
- 2014
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Abstract
- Background: Severe and fatal malaria are associated with dysregulated host inflammatory responses to infection. Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein implicated in regulating immune responses. Expression and function of CHI3L1 in malaria infection were investigated.<br />Methods: Plasma levels of CHI3L1 were quantified in a case-control study of Ugandan children presenting with Plasmodium falciparum malaria. CHI3L1 levels were compared in children with uncomplicated malaria (UM; n = 53), severe malarial anaemia (SMA; n = 59) and cerebral malaria (CM; n = 44) using the Kruskall Wallis-test, and evaluated for utility in predicting fatal (n = 23) versus non-fatal (n = 80) outcomes in severe disease using the Mann Whitney U test, receiver operating characteristic curves, and combinatorial analysis. Co-culture of P. falciparum with human peripheral blood mononuclear cells and the Plasmodium berghei ANKA experimental model of cerebral malaria were used to examine the role of CHI3L1 in severe malaria.<br />Results: In children presenting with falciparum malaria, CHI3L1 levels were increased in SMA and CM versus UM (p < 0.001). Among severe malaria cases, CHI3L1 levels at presentation predicted subsequent death (area under receiver operating characteristic curve 0.84 [95% CI 0.76-0.92]) and in combination with other host biomarkers, predicted mortality with high sensitivity (100% [85.7-100]) and specificity (81.3% [71.3-88.3]). Plasmodium falciparum stimulated CHI3L1 production by human peripheral blood mononuclear cells in vitro. CHI3L1 was increased in plasma and brain tissue in experimental cerebral malaria, but targeted Chi3l1 deletion did not alter cytokine production or survival in this model.<br />Conclusions: These data suggest that plasma CHI3L1 measured at presentation correlates with malaria severity and predicts outcome in paediatric SMA and CM, but do not support a causal role for CHI3L1 in cerebral malaria pathobiology in the model tested.
- Subjects :
- Adipokines biosynthesis
Adipokines genetics
Anemia blood
Anemia etiology
Animals
Area Under Curve
Biomarkers
Brain Chemistry
Case-Control Studies
Child
Child, Preschool
Chitinase-3-Like Protein 1
Female
Gene Expression Regulation
Glycoproteins deficiency
Glycoproteins genetics
Glycoproteins physiology
Host-Parasite Interactions
Humans
Infant
Lectins biosynthesis
Lectins genetics
Leukocytes, Mononuclear metabolism
Malaria blood
Malaria genetics
Malaria, Cerebral mortality
Malaria, Falciparum complications
Male
Mice
Mice, Inbred C57BL
Plasmodium berghei
Plasmodium falciparum physiology
Prognosis
Prospective Studies
ROC Curve
Statistics, Nonparametric
Th1 Cells immunology
Uganda epidemiology
Adipokines blood
Lectins blood
Malaria, Cerebral blood
Malaria, Falciparum blood
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2875
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Malaria journal
- Publication Type :
- Academic Journal
- Accession number :
- 25047113
- Full Text :
- https://doi.org/10.1186/1475-2875-13-279