Blood cell profiling distinguishes disease states and detects residual immune activation in ANCA-associated vasculitis

Background: Accurate, low-cost biomarkers to quantify disease activity and detect residual inflammation in ANCA-associated vasculitis (AAV) are an unmet need. Modern haematology analysers generate cell population data (CPD) and extended inflammatory indices that may capture innate/adaptive immune activation beyond conventional complete blood count (CBC). Objectives: To determine whether an integrated haematologic profile, combining CBC, CPD, and extended indices from the Sysmex XN-9000, (i) discriminates disease states in AAV (active vs remission) and (ii) reveals residual immune activation during clinical remission, including treatment-free remission (TFR). Methods: We conducted a cross-sectional study with prospectively collected samples and a nested prospective longitudinal subset. Consecutive AAV patients were sampled in active disease or clinical remission; healthy controls (HC) were healthy blood donors processed under identical pre-analytical conditions. Key prespecified markers included immature granulocytes (IG), neutrophil activation (NEUT-RI, NE-SFL), and composite ratios (NLR/PLR/MLR), alongside leukocyte structural indices. Primary analyses compared active vs remission and remission vs HC; the longitudinal subset evaluated within-patient change (active to remission). Non-parametric tests were used for group comparisons; multivariable models adjusted for age, sex, ANCA status at sampling, treatment exposure, and disease/remission duration. Results: We analysed 99 unique AAV patients (28 active, 71 remission), including 13 paired patients resampled in remission; 258 HC were included. Active disease showed a robust myeloid-high / lymphoid-low signature: higher WBC and neutrophils, elevated NLR/PLR/MLR, increased IG, and higher NEUT-RI/NE-SFL, with relative lymphopenia; platelets were higher and haemoglobin lower, compatible with inflammation-associated thrombocytosis and anaemia. In the paired subset, these abnormalities improved on transition to remission (declines in neutrophils, NLR/PLR and IG; reductions in NEUT-RI/NE-SFL), confirming a state-linked pattern rather than between-subject effect. Despite quiescent symptoms, remission (including treatment-free remission) retained residual activation compared to HC: higher WBC/neutrophils, elevated NLR/PLR/MLR, increased IG, and modest shifts in leukocyte structural indices. In multivariable analyses, disease state remained the principal determinant of neutrophils, IG, NEUT-RI/NE-SFL (all p<0.01), while adaptive-leaning indices (AS-LYMP/RE-LYMP/HFLC) varied with ANCA positivity and treatment (notably rituximab), indicating therapy-sensitive modulation of lymphocyte dynamics. Conclusions: Integrated haematologic profiling from a routine analyser identifies a state-dependent inflammatory signature in active AAV and uncovers low-grade residual immune activation during clinical remission, including treatment-free remission. Markers linked to innate activation (IG, NEUT-RI/NE-SFL, NLR/PLR/MLR) improve with remission yet incompletely normalise vs HC, whereas adaptive indices are more therapy/ANCA-dependent. These readily available parameters could complement standard biomarkers for monitoring, help flag residual activity, and support risk-stratified care.