Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2022 Mar 2;61(3):1158-1165.
doi: 10.1093/rheumatology/keab508.

Inorganic pyrophosphate is reduced in patients with systemic sclerosis

Vivien M Hsu  1 , Eszter Kozák  2 , Qiaoli Li  3 , Márta Bocskai  4 , Naomi Schlesinger  1 , Ann Rosenthal  5 , Scott T McClure  6   7 , László Kovács  4 , László Bálint  8 , Szilvia Szamosi  9 , Gabriella Szücs  9 , Mary Carns  10 , Kathleen Aren  10 , Isaac Goldberg  10 , András Váradi  2 , John Varga  10   11
Affiliations
Comparative Study

Inorganic pyrophosphate is reduced in patients with systemic sclerosis

Vivien M Hsu et al. Rheumatology (Oxford). .

Abstract

Objective: The pathogenesis of calcinosis cutis, a disabling complication of SSc, is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis.

Methods: Subjects with SSc and age-matched controls without SSc were recruited from the outpatient rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5' phosphosulfate.

Results: Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: P = 0.003; Hungarian: P < 0.001).

Conclusions: Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.

Keywords: SSc; calcinosis; ectopic mineralization; hydroxyapatite; inorganic pyrophosphate.

PubMed Disclaimer

Figures

<sc>Fig</sc>. 1
Fig. 1
Distribution of PPi values by type of SSc for the US (left) and Hungarian (right) cohorts
<sc>Fig</sc>. 2
Fig. 2
Distribution of PPi values by calcinosis status for the US (left) and Hungarian (right) cohorts
See this image and copyright information in PMC

References

    1. Giachelli CM. Ectopic mineralization: gathering hard facts about soft tissue mineralization. Am J Pathol 1999;154:671–5. - PMC - PubMed
    1. Budoff MJ, Shaw LJ, Liu ST. et al. Long-term prognosis associated with coronary mineralization: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860–70. - PubMed
    1. Steen VD, Ziegler GL, Rodnan GP. et al. Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum 1984;27:125–31. - PubMed
    1. Fredi M, Bartoli F, Cavazzana I. et al. Calcinosis in poly-dermatomyositis: clinical and laboratory predictors and treatment options. Clin Exp Rheumatol 2017;35:303–8. - PubMed
    1. Nazir L, Saeed M.. The calcium invasion: calciphylaxis in lupus. J Pak Med Assoc 2015;65:427–8. - PubMed

Publication types