035. CANDIDATE BIOMARKERS IN ANCA-ASSOCIATED VASCULITIS IDENTIFIED USING A PROTEOMIC APPROACH

Abstract

Background/Purpose: Concentrations of many circulating proteins are elevated during severe, active ANCA‐associated vasculitis (AAV). Finding biomarkers associated with milder disease, a more clinically relevant need, has proved challenging. In addition, some biomarkers may be directly affected by glucocorticoids. Methods: 30 patients with AAV participating in a longitudinal cohort were studied. Serum samples from 2 visits were used for this study: i) a visit during active disease and when off prednisone; and ii) a visit approximately 3 months later when in clinical remission and on prednisone. A proteomic approach (SOMAscan, SomaLogic, Boulder, CO, USA) was used to assess more than 1000 circulating proteins simultaneously. Using Wilcoxon signed rank tests, a randomly selected subcohort of 15 patients was analyzed first, and markers significant at p <0.01 were then analyzed in the remaining sub‐cohort of 15 patients, with p <0.05 regarded as validation. WebGestalt was used to test for enrichment in components of functional pathways. Results: The cohort included 23 patients with GPA, 5 with EGPA, and 2 with MPA. Mean age was 52, and 18 were female. Thirteen were taking a non‐steroid immunosuppressive drug at the time of flare, and 21 afterward. Disease activity was relatively low: physician global assessment of severity on a 0‐10 scale had a mean of 3.2 (median 3, range 1‐7), and only 7 patients had a 'major' manifestation by BVAS/WG. Fourteen proteins were validated as associated with active disease (Table 1). Few of these markers have been previously identified in vasculitis, and only one (thrombospondin, TSP) in AAV. Four markers (CCL3/Mip‐1a, CCL15/Mip‐5, TNFRSF9/4‐1BB, prolactin) are associated with the KEGG pathway Cytokine‐cytokine receptor interaction. Conclusion: In a cohort of patients with active but relatively mild AAV, 14 serum proteins were associated with significant change after successful treatment with prednisone. Thirteen of these markers have not been reported in AAV. These proteins, all of which are measurable by commercial immunoassays, are candidates for further study in real‐world cohorts of partially‐treated patients with AAV with mildly active disease. (Table Presented) .