Haptoglobin-related protein in human plasma correlates to haptoglobin concentrations and phenotypes

Maria Kløjgaard Skytthe, Anna Lahn Sørensen, Dorle Hennig, Maria Boysen Sandberg, Lars Melholt Rasmussen, Peter Højrup, Holger Jon Møller, Karsten Skjødt, Søren Kragh Moestrup*, Jonas Heilskov Graversen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Haptoglobin-related protein (Hpr) is a plasma protein with high sequence similarity to haptoglobin (Hp). Like Hp, Hpr also binds hemoglobin (Hb) with high affinity, but it does not bind to the Hb-Hp receptor CD163 on macrophages. The Hpr concentration is markedly lower than Hp in plasma and its regulation is not understood. In the present study, we have developed non-crossreactive antibodies to Hpr to analyze the Hpr concentration in 112 plasma samples from anonymized individuals and compared it to Hp. The results show that plasma Hpr correlated with Hp concentrations (rho = 0.46, p =.0001). Hpr accounts for on average 0.35% of the Hp/Hpr pool but up to 29% at low Hp levels. Furthermore, the Hpr concentrations were significantly lower in individuals with the Hp2-2 phenotype compared to those with the Hp2-1 or Hp1-1 phenotypes. Experimental binding analysis did not provide evidence that Hpr associates with Hp and in this way is removed via CD163. In conclusion, the Hpr concentration correlates to Hp concentrations and Hp-phenotypes by yet unknown mechanisms independent of CD163-mediated removal of Hb-Hp complexes.

Original languageEnglish
JournalScandinavian Journal of Clinical and Laboratory Investigation
Issue number6
Pages (from-to)461-466
Publication statusPublished - Sept 2022


  • Haptoglobins
  • blood proteins
  • enzyme-linked immunosorbent assay
  • hemoglobins
  • immunoassay


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