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Suppression of a novel hematopoietic mediator in children with severe malarial anemia

Christopher C Keller1, Collins Ouma, Yamo Ouma

  • 1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA.

Infection and Immunity
|June 17, 2009
PubMed

Insights

Severe malarial anemia in children is linked to reduced levels of stem cell growth factor (SCGF). Malarial pigment (hemozoin) exposure suppresses SCGF, potentially impairing red blood cell production and contributing to anemia.

Area of Science:

  • Hematology
  • Immunology
  • Pediatrics

Background:

  • Severe malarial anemia (SMA) is a major cause of death in children in holoendemic Plasmodium falciparum transmission areas.
  • The role of soluble mediators in erythropoiesis regulation and their contribution to SMA pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the role of stem cell growth factor (SCGF), also known as C-type lectin domain family member 11A (CLEC11A), in the development of SMA.
  • To determine the relationship between SCGF levels, malarial pigment (hemozoin), and erythropoiesis in children with SMA.

Main Methods:

  • Investigated SCGF/CLEC11A gene expression in response to malarial pigment (PfHz) in cultured peripheral blood mononuclear cells (PBMCs).
  • Measured circulating SCGF levels in Kenyan children (n=90, aged 3-36 months) with varying degrees of malarial anemia.
  • Correlated SCGF levels with hemoglobin, reticulocyte production index (RPI), and PfHz levels.

Main Results:

  • PfHz exposure decreased SCGF/CLEC11A transcriptional expression in a time-dependent manner.
  • Children with SMA exhibited suppressed circulating SCGF levels (P=0.001) and reduced SCGF expression in PBMCs (P=0.004).
  • Circulating SCGF positively correlated with hemoglobin levels (r=0.241, P=0.022) and RPI (r=0.280, P=0.029).
  • SCGF was decreased in children with reduced erythropoiesis (RPI < 2) and elevated PfHz levels.

Conclusions:

  • Phagocytosis of malarial pigment (PfHz) leads to decreased SCGF production.
  • Reduced SCGF may contribute to impaired erythropoiesis and the development of severe malarial anemia in children.

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