Serum citrullinated histone H3 as a biomarker of disease activity and renal outcome in microscopic polyangiitis and granulomatosis with polyangiitis

Abstract

Background Citrullinated histone H3 (CitH3), a hallmark component of neutrophil extracellular traps, has emerged as a circulating indicator of pathological neutrophil activation. We evaluated the utility of serum CitH3 as a biomarker for disease activity and risk of end-stage kidney disease (ESKD) development in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods A total of 65 patients with MPA and GPA were included. At diagnosis, serum CitH3 levels were measured and disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). Correlation between serum CitH3 level and BVAS was assessed using Pearson&apos;s correlation coefficient. Discriminatory performance of serum CitH3 for severe disease (BVAS >= 20) and low disease activity states (BVAS <= 3) was evaluated using receiver operating characteristic curve analysis. The association between serum CitH3 level and ESKD risk was assessed using multivariable Cox regression analysis. Results Serum CitH3 levels significantly correlated with BVAS (r = 0.393, p = 0.001). Moreover, serum CitH3 demonstrated excellent discriminatory performance (area under the curve [AUC] 0.905, 95% confidence interval [CI] 0.825-0.984, p < 0.001) for severe disease (BVAS >= 20), and acceptable discriminatory performance (AUC 0.703, 95% CI 0.558-0.848, p = 0.013) for low disease activity states (BVAS <= 3). During a mean follow-up of 38.3 +/- 32.8 months, eight (12.3%) patients developed ESKD. After adjusting for age and serum creatinine, higher serum CitH3 levels were independently associated with an increased risk of ESKD (adjusted hazard ratio 1.181, 95% CI 1.033-1.352, p = 0.015). Conclusion Serum CitH3 correlated with disease activity, demonstrated strong discriminatory performance for severe disease and acceptable discriminatory performance for low disease activity states, and was associated with an increased risk of ESKD. These findings support serum CitH3 as a potential biomarker for identifying severe disease and low disease activity states, and stratifying ESKD risk in MPA and GPA.