title: Individual variation in levels of haptoglobin-related protein in children from Gabon.
abstract: BACKGROUND
  Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of high-density lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas.
  
  
  RESULTS
  We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP.
  
  
  CONCLUSIONS
  Individual variation in Hpr levels was related to Hp level, Hp genotype, demographics, malaria status and the APR. The strong correlations between plasma levels of Hp and Hpr suggest that they are regulated by similar mechanisms. These population-based observations indicate that a more dynamic view of the relative roles of Hpr and Hpr-Hb complexes needs to be considered in understanding innate immunity to African trypanosomes and possibly other pathogens including the newly discovered Plasmodium spp of humans and primates.
authors.affiliation: Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Imrie
authors.forename: Freya J I
authors.initials: FJ
authors.lastname: Fowkes
authors.forename: Florence
authors.initials: F
authors.lastname: Migot-Nabias
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hajduk
authors.forename: Karen P
authors.initials: KP
authors.lastname: Day
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D005260:Female; D005681:Gabon; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008288:Malaria / Q000097:blood / Q000635:transmission; D008297:Male; D011110:Polymorphism, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C058632:HPR protein, human; D006242:Haptoglobins; D006454:Hemoglobins; D008075:Lipoproteins, HDL; C434063:TLF1 protein, human; D002097:C-Reactive Protein