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. 2019 Dec;7(24):798.
doi: 10.21037/atm.2019.12.73.

Plasma inorganic pyrophosphate and alkaline phosphatase in patients with pseudoxanthoma elasticum

Ana María Sánchez-Tévar  1 , María García-Fernández  2 , Belén Murcia-Casas  3 , José Rioja-Villodres  1   4 , Juan Luis Carrillo  3 , Marta Camacho  5 , Matthias Van Gils  6   7 , Miguel Angel Sánchez-Chaparro  1   3   4 , Olivier Vanakker  6   7 , Pedro Valdivielso  1   3   4
Affiliations

Plasma inorganic pyrophosphate and alkaline phosphatase in patients with pseudoxanthoma elasticum

Ana María Sánchez-Tévar et al. Ann Transl Med. 2019 Dec.

Abstract

Background: Inorganic pyrophosphate (PPi) plays a major role inhibiting dystrophic calcification. The aim was to analyze levels of PPi in patients having pseudoxanthoma elasticum (PXE), and controls as well as the enzymes who regulate the PPi plasma concentration.

Methods: We collected fasting blood samples from PXE patients and age- and sex-matched controls in ethylenediamine tetraacetic acid (EDTA) and citrate-theophylline-adenosine-dipyridamole (CTAD) containing tubes. We measured PPi, ENPP1 mass and activity, alkaline phosphatase (AP) and tissue non-specific alkaline phosphatase (TNAP), CD73 and Human Platelet Factor-4 (CXCL4).

Results: PPi in EDTA and CTAD samples were lower in PXE subjects than in controls (1.11±0.26 vs. 1.43±0.41 µM/L and 0.35±0.15 vs. 0.61±0.18 µM/L respectively, P<0.05). TNAP and liver TNAP activities were also higher in PXE than in controls (80.3±27.0 vs. 63.3±16.4 UI/L and 25.6±14.9 vs. 12.9±9.2 UI/L respectively, P<0.05). ENPP1 mass and activity as well as CD73 were almost identical. There was a weak but significant inverse correlation between TNAP activity and PPi levels (Pearson correlation -0.379, P<0.05) in both groups.

Conclusions: High TNAP activity seems to contribute to low plasma levels of PPi in subjects with PXE, reinforcing the idea that pharmacological reduction of TNAP activity may help to reduce dystrophic calcification in PXE patients.

Keywords: CD73; ENPP1; Pseudoxanthoma elasticum (PXE); alkaline phosphatase (AP); calcification; inorganic pyrophosphate (PPi); non-specific tissue alkaline phosphatase (TNAP).

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Plasma levels of PPi, Alkaline phosphatase and tissue-non specific alkaline phosphatase, ENPP1 activity and mass, and 5’Nucleotidase activity, in PXE patients and controls. ##, P<0.05. PPi, inorganic pyrophosphate; ePPi, ppi measured in EDTA samples; cPPi, PPi measured in CTAD samples; ALP, alkaline phosphatase activity; TNAP, tissue non-specific alkaline phosphatase; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; PXE, pseudoxanthoma elasticum.
Figure 2
Figure 2
Pearson’s coefficient between TNAP activity and cPPi both controls (blue square) and PXE (red triangles) groups. PXE, pseudoxanthoma elasticum; cPPi, inorganic pyrophosphate measured in CTAD samples; TNAP, tissue non-specific alkaline phosphatase.
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