Inorganic pyrophosphate is reduced in patients with systemic sclerosis.

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.

• Authors: Vivien M Hsu, Eszter Kozák, Qiaoli Li, Márta Bocskai, Naomi Schlesinger, Ann Rosenthal, Scott T McClure, László Kovács, László Bálint, Szilvia Szamosi, Gabriella Szücs, Mary Carns, Kathleen Aren, Isaac Goldberg, András Váradi, John Varga
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 61 Issue 3 Pg. 1158-1165 (03 02 2022) ISSN: 1462-0332 [Electronic] England
• PMID: 34152415 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Diphosphates
• diphosphoric acid

Topics

• Adult
• Aged
• Calcinosis (blood, etiology)
• Diphosphates (blood)
• Female
• Humans
• Male
• Middle Aged
• Scleroderma, Systemic (blood, complications)