Background/Purpose: Angiopoietin-2 (Ang-2) has emerged as a key mediator of endothelial cell activation. Ang-1 and Ang-2 are antagonistic ligands which bind with similar affinity to the extracellular domain of the tyrosine kinase with Ig-like and epidermal growth factor-like domains 2 (Tie-2) receptor, which is almost exclusively expressed by endothelial cells. Ang-1/Tie-2 signalling maintains vessel integrity, inhibits vascular leakage, suppresses inflammatory gene expression and prevents recruitment and transmigration of leukocytes. In contrast, binding of Ang-2 disrupts protective Ang-1/Tie-2 signalling and facilitates endothelial inflammation. Recently, serum Ang-2 levels have been reported to be elevated in autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, and ANCA-associated vasculitis (AAV). The purpose of this study is to examine the serum Ang-2 levels in patients with AAV, and investigate the relationship with the clinical and laboratory findings.
Methods: Fifty-nine patients with AAV (microscopic polyangitis (MPA, n=27), granulomatosis with polyangitis (GPA, n=15), Churg-Strauss syndrome (CSS, n=14), others (n=3)), who had been referred to Niigata University Medical and Dental Hospital between 2000 and 2011, were enrolled in this study. Written informed consent was obtained from each participant. The patients were divided into 2 groups according to their disease activities using Birminghamvasculitis activity score (BVAS) (active disease group (AD group, n=45) and remission disease group (RD group, n=14)) Serum Ang-2 levels and laboratory findings were examined in each subject, and the data were compared between these 2 groups. The data from all subjects were analyzed using Spearman’s rank correlation coefficient to determine the relationship with serum Ang-2 levels. Next, the patients with AD group were divided into 2 groups in accordance with their stages of chronic kidney diseases (CKD) (CKD<3 group, n=19, and CKD≥3 group, n=26), and the data were compared to examine the impact of renal function in this study.
Results: The serum Ang-2 level, C-reactive protein (CRP), white blood cell count, and urinary protein excretion were significantly higher in AD group compared with those in RD group. In Spearman’s rank correlation coefficient analysis using data from all subjects, the serum Ang-2 level was positively correlated with BVAS (r=0.62, p＜0.0001), CRP (r=0.47, p=0.0003), serum creatinine (Cr) (r=0.38, p=0.005), and urinary protein excretion (UP) (r=0.55, p＜0.0001), and negatively correlated with estimated glomerular filtration rate (r=-0.37, p=0.005). In the next analysis, patients in CKD≥3 were significantly elder and BVAS was significantly higher compared to those with patients in CKD<3 group. Ang-2 was elevated in CKD≥3 group without statistical significance. In Spearman’s rank correlation coefficient analysis, Ang-2 was positively correlated with CRP and BVAS in CKD<3 group, while it was correlated with UP, e-GFR, Cr, and CRP in CKD≥3 group.
Conclusion: Serum Ang-2 level was strongly correlated with the disease activity and renal function in AAV. These results indicated the possible role of Ang-2 in the development of AAV through endothelial injuries.
Disclosure:
Y. Wada,
None;
H. Sato,
None;
T. Nakatsue,
None;
S. Murakami,
None;
T. Kuroda,
None;
M. Nakano,
None;
I. Narita,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-angiopoietin-2-level-reflects-the-disease-activity-and-renal-function-in-antineutrophilic-cytoplasmic-antibody-associated-vasculitis/