Document Detail

Individual variation in levels of haptoglobin-related protein in children from Gabon.
MedLine Citation:
PMID:  23185445     Owner:  NLM     Status:  MEDLINE    
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.
METHODS AND PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
Heather J Imrie; Freya J I Fowkes; Florence Migot-Nabias; Adrian J F Luty; Philippe Deloron; Stephen L Hajduk; Karen P Day
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-20
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-05-30     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e49816     Citation Subset:  IM    
Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom.
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MeSH Terms
Antigens, Neoplasm* / blood,  genetics
C-Reactive Protein / metabolism
Haptoglobins / genetics,  metabolism*
Hemoglobins / chemistry,  metabolism
Lipoproteins, HDL / blood,  chemistry,  genetics,  metabolism
Malaria* / blood,  transmission
Polymorphism, Genetic*
Trypanosoma brucei brucei / genetics,  metabolism
Grant Support
041354//Wellcome Trust; 047069/Z/96/Z//Wellcome Trust; AI039099/AI/NIAID NIH HHS
Reg. No./Substance:
0/Antigens, Neoplasm; 0/HPR protein, human; 0/Haptoglobins; 0/Hemoglobins; 0/Lipoproteins, HDL; 0/TLF1 protein, human; 9007-41-4/C-Reactive Protein

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