Inorganic pyrophosphate is reduced in patients with systemic sclerosis
Autor: | András Váradi, László Kovács, Naomi Schlesinger, Gabriella Szücs, Qiaoli Li, Kathleen Aren, Eszter Kozák, Vivien Hsu, Isaac Goldberg, Márta Bocskai, John Varga, Scott T. McClure, Bálint Bálint László, Ann K. Rosenthal, Mary Carns, Szilvia Szamosi |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Gastroenterology Article Calcinosis cutis Pathogenesis 03 medical and health sciences 0302 clinical medicine Rheumatology Inorganic pyrophosphate Calcinosis Internal medicine medicine Humans Pharmacology (medical) skin and connective tissue diseases Aged 030203 arthritis & rheumatology Scleroderma Systemic integumentary system business.industry Middle Aged medicine.disease Pathophysiology Diphosphates 030104 developmental biology Cohort Female Complication business |
Zdroj: | Rheumatology (Oxford) |
ISSN: | 1462-0332 1462-0324 |
Popis: | 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 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. |
Databáze: | OpenAIRE |
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