Article Text

PDF
SAT0275 Serum Proteins as Biomarkers of Systemic Necrotizing Vasculitis (SNV)
  1. L. Petelytska,
  2. O. Iaremenko,
  3. K. Iaremenko
  1. Bogomolets National Medical University, Kyiv, Ukraine

Abstract

Background SNV are severe inflammatory disorders with highly variable course of disease after initial treatment. New biomarkers are needed for SNV because the existing markers such as anti-neutrophil cytoplasmic antibodies (ANCA) titres and non-specific markers of inflammation such as C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) have limited value in assessment of vasculitis activity.

Objectives To identify circulating proteins those distinguish active SNV from responders to treatment and from healthy controls.

Methods Four serum proteins (alpha actin 2 (α-SMA), endothelin-1 (ET-1), B-cell activating factor (BAFF) and elastin) representing difference aspects of pathogenesis of vasculitis, CRP and ESR were measured in 48 pts with SNV (granulomatosis with polyangiitis – 22, eosinophilic granulomatosis with polyangiitis – 9, microscopic polyangiitis – 6, polyarteritis nodosa – 11) and 26 healthy controls. The 48 pts included 18 male and 30 female with median age 49; 24 were positive for c-ANCA and 11 for p-ANCA. At screening, 9 pts were without any treatment, 26 pts were receiving glucocorticoids (GCs) and 13 pts were receiving some cytotoxic agents and GCs. Clinical activities of pts were calculated according to the Birmingham Vasculitis Activity Score (BVAS) before treatment and at screening. The outcomes of this study were the differences in marker levels between pts with active SNV without treatment (n=9; group 1), pts with responding to treatment (decrease BVAS in 5 and more points) (n=27; group 2), pts with non-adequate response to treatment (without decrease BVAS in 5 and more points) (n=12; group 3) and healthy controls estimated by analysis of the absolute changes in marker levels and the areas under receiver operating characteristic (ROC) curves. Correlation between pairs of markers was measured using Spearman correlation coefficients.

Results The mean BVAS in group 1 was 27±4.6, in group 2-15±5.7 and in group 3-23±7.3. There were significant differences in levels of ET-1 (increased twofold) and α-SMA (increased five-fold) between group 1 and controls. The levels of elastin, ET-1 and α-SMA were significantly lower (by 14%, 58% and 75% respectively) in group 2 compared with group 1, but did not distinguish from the controls. In group 3 levels of ET-1 and α-SMA showed significant increases compared with controls (by 11% and three-fold respectively) and group 2 (by 15% and 157% respectively); the level of ET-1 was also significantly lower (by 52%) compared with group1. There were no differences in levels of BAFF between groups. ROC analysis indicated that level of α-SMA better than the other markers discriminated active SNV without treatment from responding to treatment (AUC>0.83) and from controls (AUC>0.96). Correlation between this marker and ESR was low (r=0.37). There were no correlations between α-SMA and CRP, p-ANCA, c-ANCA and negative moderate correlation with doses of GCs (r=–0.51).

Conclusions The levels of serum ET-1 and α-SMA are elevated in severe active SNV. There are significant differences in levels of those markers between pts with responding to treatment and pts with non-adequate response to treatment. According to ROC analysis α-SMA distinguishes pts with active SNV without treatment from responders to treatment and healthy controls better than the other markers studied. This protein is particularly promising candidate for future studies addressing to monitoring of SNV courses.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2961

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.