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

Abstract

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.

Keywords:

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

Acknowledgments

The authors thank Signe Marie Andersen, Malene Bille Jørgensen, Jette Hvelplund, and Maiken Lumby Henriksen for excellent technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Danish National Research Foundation under Grant DNRF141 to Center for Functional Genomics and Tissue Plasticity (ATLAS); the Danish Council for Independent Research under Grant 4004-001; and Novo Nordisk Foundations under Grant NNF14OC0011537.