Session Information
Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Pentraxin 3 (PTX3) is a multi-functional pattern recognition protein involved in inflammation, extracellular matrix deposition, and suppression of neovascularization mediated by fibroblast growth factor-2 (FGF2). Several lines of recent evidence suggest that PTX3 is constitutively overexpressed in fibroblasts and endothelial cells derived from systemic sclerosis (SSc) patients. The aim of this study is to examine roles of PTX3 in pathogenic processes of SSc.
Methods: We enrolled 171 patients with SSc and 19 age- and sex-matched healthy controls. Circulating levels of PTX3 and FGF2 were measured by enzyme immunoassay and their correlations with SSc-related organ involvement were evaluated. Univariate and multivariate analysis was conducted to investigate if PTX3 and FGF2 were correlated with the presence or future development of vascular manifestations, including digital ulcer (DU) and pulmonary arterial hypertension (PAH). Circulating CD34+CD133+CD309+ endothelial progenitor cells (EPCs) were enumerated by flow cytometry. Effects of recombinant PTX3 on EPC differentiation were evaluated in pro-angiogenic cultures of mouse bone marrow mononuclear cells, followed by colony formation assay.
Results: PTX3 and FGF2 were significantly increased in SSc patients than in healthy controls (P < 0.001 and P = 0.001, respectively). When PTX3 and FGF2 levels were compared between two groups stratified by the presence or absence of individual organ involvement, PTX3 was increased in SSc patients with DU or PAH than in those without (P < 0.001 and P = 0.006, respectively), while FGF2 was reduced in patients with PAH (P < 0.001). Multivariate analysis revealed that elevated PTX3 was an independent parameter associated with the presence of DU (odds ratio (OR) = 1.50, P < 0.001) and PAH (OR = 1.23, P = 0.002), and was useful in predicting future occurrence of DU (hazard ratio = 1.12, P = 0.04). In contrast, reduced FGF2 was independently associated with the presence of PAH (OR = 0.91, P = 0.02). EPC counts were significantly reduced in patients with DU or PAH than in those without (P = 0.003 and 0.003, respectively), and were correlated negatively with circulating PTX3 concentration (r = -0.53, P < 0.001) and a PTX3/FGF2 ratio (r = -0.35, P = 0.003). Finally, exogenous PTX3 significantly inhibited differentiation of EPCs from mouse bone marrow stem cells in vitro.
Conclusion: PTX3 was elevated in circulation of SSc patients and was a useful biomarker that predicts the presence of DU and PAH as well as future development of DU. In addition, continuous exposure to a high PTX3 concentration may contribute to SSc vasculopathy through inhibition of vasculogenesis by exerting its suppressive effects on FGF2.
Disclosure:
Y. Shirai,
None;
Y. Okazaki,
None;
Y. Inoue,
None;
Y. Tamura,
None;
H. Yasuoka,
None;
T. Takeuchi,
None;
M. Kuwana,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-pentraxin-3-in-patients-with-systemic-sclerosis-associations-with-vascular-manifestations-and-defective-vasculogenesis/