Current and novel biomarkers in anti-neutrophil cytoplasm-associated vasculitis

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is characterized by a variable disease course, with up to 50% of patients having one relapse within 5 years and many progressing to end-stage organ damage despite modern treatment strategies. Moreover, complications arising from treatment dominate the causes of mortality and morbidity both early and late during disease, especially in the elderly and those with severe renal involvement, and there is additional uncertainty as to how long treatment should be continued. There is, therefore, an urgent clinical need to identify robust biomarkers to better predict treatment responses, risk of disease relapse and eventual complete clinical and immunological quiescence. To date, no such biomarkers exist, but better understanding of disease pathogenesis and the underlying immune dysfunction has provided some potential candidates linked to the discovery of new antibodies, different leukocyte activation states, the role of the alternative complement pathway and markers of vascular activation. With all promising new biomarkers, there is the need to rapidly replicate and validate early findings using large biobanks of samples that could be brought together by leaders in the field

The association of serum calprotectin (S100A8/S100A9) levels with disease relapses in PR3-ANCA-associated vasculitis

OBJECTIVES: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in AAV. This study investigated serum S100A8/A9 levels as a biomarker predicting future relapse in a large cohort of patients with severe ANCA-associated vasculitis (AAV). METHODS: Serum levels of S100A8/A9 were measured at baseline, months 2, and 6 following treatment initiation in 144 patients in the RAVE trial (cyclophosphamide/azathioprine vs. rituximab for induction of remission) who attained complete remission. RESULTS: Patients were divided into 4 groups: PR3-ANCA with (n=37), and without (n=56) relapse, and MPO-ANCA with (n=6) and without (n=45) relapse. Serum S100A8/A9 levels decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between relapsers and non-relapsers in the PR3-AAV group (p=0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 between baseline and month 2 (p=0.006) and baseline and month 6 (p=0.0099) for all patients. Subgroup analysis demonstrated it was patients treated with rituximab and who increased levels of S100A8/A9 who were at greatest risk of future relapse (p=0.028). CONCLUSION: An increase in serum S100A8/A9 by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with rituximab at higher risk of relapse by 18 months. As rituximab is increasingly used for remission induction in relapsing PR3-ANCA patients, S100A8/A9 may assist in identifying those patients requiring more intensive or prolonged treatment