Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti‐neutrophil cytoplasmic antibodies

Summary Anti‐neutrophil cytoplasmic antibodies ( ANCA ) are thought to be pathogenic in ANCA ‐associated vasculitis ( AAV ) by stimulating polymorphonuclear leucocytes ( PMN s) to degranulate and produce reactive oxygen species ( ROS ). The aim of this study was to investigate if PMN s from AAV patients are stimulated more readily by ANCA compared with PMN s from healthy controls ( HC s). Differences in ANCA characteristics that can account for different stimulation potential were also studied. PMN s from five AAV patients and five HC s were stimulated with 10 different immunoglobulins ( Ig)G s, purified from PR 3– ANCA ‐positive patients, and ROS production, degranulation and neutrophil extracellular trap ( NET ) formation was measured. ANCA levels, affinity and clinical data of the AAV donors were recorded. The results show that PMN s from AAV patients produce more intracellular ROS ( P  = 0·019), but degranulate to a similar extent as PMN s from HC s. ROS production correlated with NET formation. Factors that may influence the ability of ANCA to activate PMN s include affinity and specificity for N ‐terminal epitopes. In conclusion, our results indicate that PMN s from AAV patients in remission behave quite similarly to HC PMN s, with the exception of a greater intracellular ROS production. This could contribute to more extensive NET formation and thus an increased exposure of the ANCA autoantigens to the immune system.