Background/Purpose: Angiopoietin-1 (Ang-1) and Angiopoietin-2 (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. The purpose of this study is to examine the serum Angpt1 and Angpt2 levels in patients with AAV, and explore the utility as biomarkers.

Methods: Seventy-one patients who had been diagnosed as AAV and referred to Niigata University Medical and Dental Hospital between 2009 and 2017, were participated in this study. Serum Ang-1 and Ang-2 levels were measured by enzyme-linked immunosorbent assay, before the initiation of remission-induction therapy. Laboratory findings, disease activity using Birmingham vasculitis activity score (BVAS) at the time of diagnosis, and patients’ kidney and overall prognosis at August 2017, were corrected from patients’ clinical records. The correlations between these findings and serum Ang-1, Ang-2 levels, and Ang-1/Ang-2 ratio were analyzed by Spearman correlation coefficient and stepwise multiple regression analysis. A value of p <0.05 was taken to indicate statistical significance.

Results: In Spearman correlation coefficient analysis, serum Ang-1 was positively correlated with estimated glomerular filtration ratio (eGFR) (r=0.3979、p=0.0006) and C-reactive protein (0.2574, p=0.0302), and negatively correlated with serum creatinine (Cr) (r=-0.3438、p=0.0033), initiation of dialysis therapy (r=-0.2559, p=0.0312), and death (r=-03057, p=0.0095). Serum Ang-2 was positively correlated with age (r=0.2466, p=0.0382), BVAS (r=0.3090、p=0.0087), serum Cr (r=0.3945、p=0.0007), and negatively correlated with eGFR (r=-0.4278、p=0.0002). The Ang-1/Ang-2 ratio was positively correlated with eGFR(r=0.5715、p<0.0001), and negatively correlated with age (r=-0.2359, p=0.0476), BVAS (r=-0.3456, p=0.0032), Cr (r=-0.5234), 24-hour urinary protein excretion (r=-0.2863, p=0.0155), initiation of dialysis therapy (r=-0.3251, p=0.0057), and death (r=-0.2556, p=0.0314). In stepwise multiple regression analysis, eGFR was selected as a positive independent variable for serum Ang-1 levels (beta=0.4138, p=0.0003) and Ang-1/ Ang-2 ratio (beta=0.4305, p=0.00017), whereas initiation of dialysis therapy was selected as a positive independent variable (beta=0.2803, p=0.033), and UP/Cr (beta=-0.3908, p=0.0043) and eGFR (beta=-0.4897, p=0.0001) were selected as negative independent variables for serum Ang-2 levels.

Conclusion: These findings showed the protective effect of kidney functions for Ang-1 and the utility of Ang-2 as a predictive factor for kidney prognosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-utility-of-serum-angiopoietin-1-and-angiopoietin-2-in-patients-with-anti-neutrophil-cytoplasmic-autoantibody-associated-vasculitis/