Elevated Levels of Pentraxin 3 in Systemic Sclerosis: Associations With Vascular Manifestations and Defective Vasculogenesis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 67; no. 2; pp. 498 - 507
• Main Authors: Shirai, Yuichiro, Okazaki, Yuka, Inoue, Yumiko, Tamura, Yuichi, Yasuoka, Hidekata, Takeuchi, Tsutomu, Kuwana, Masataka
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2015
• Subjects: Adult; Aged; Biomarkers - blood; Bone marrow; C-Reactive Protein - metabolism; Case-Control Studies; Endothelium, Vascular - physiopathology; Female; Fibroblast Growth Factor 2 - blood; Fingers; Humans; Hypertension, Pulmonary - epidemiology; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - physiopathology; Incidence; Male; Medical research; Middle Aged; Multivariate Analysis; Neovascularization, Pathologic - physiopathology; Scleroderma, Systemic - blood; Scleroderma, Systemic - complications; Scleroderma, Systemic - physiopathology; Sensitivity and Specificity; Serum Amyloid P-Component - metabolism; Time Factors; Ulcer - epidemiology; Ulcer - etiology; Ulcer - physiopathology
• ISSN: 2326-5191; 2326-5205; 2326-5205
• DOI: 10.1002/art.38953

Objective To clarify the role of pentraxin 3 (PTX3), a multifunctional pattern recognition protein that can suppress fibroblast growth factor 2 (FGF‐2), in systemic sclerosis (SSc)–related vasculopathy. Methods We assessed 171 SSc patients and 19 age‐ and sex‐matched healthy control subjects. Circulating PTX3 and FGF‐2 levels were measured by enzyme immunoassay, and CD34+CD133+CD309+ endothelial progenitor cells (EPCs) were counted by flow cytometry. Correlations between PTX3 and FGF‐2 and the presence or future development of vascular manifestations, including digital ulcers and pulmonary arterial hypertension (PAH), were identified by univariate and multivariate analysis. The effect of PTX3 on EPC differentiation was evaluated in proangiogenic cultures of mouse bone marrow cells in combination with colony formation assay. Results Circulating PTX3 and FGF‐2 levels were significantly higher in SSc patients than in healthy control subjects. PTX3 was elevated in SSc patients who had digital ulcers or PAH, while FGF‐2 was reduced in SSc patients with PAH. Multivariate analysis identified elevated PTX3 as an independent parameter associated with the presence of digital ulcers and PAH, and PTX3 levels were a useful predictor of future occurrences of digital ulcers. Reduced FGF‐2 was independently associated with the presence of PAH. EPC counts were significantly lower in patients with digital ulcers or PAH and correlated negatively with circulating PTX3 concentrations. Finally, PTX3 inhibited EPC differentiation in vitro. Conclusion In SSc patients, exposure to high concentrations of PTX3 may suppress EPC‐mediated vasculogenesis and promote vascular manifestations such as digital ulcers and PAH.