Incidence and disease associations of a proteinase 3-antineutrophil cytoplasmic antibody idiotype (5/7 Id) whose antiidiotype inhibits proteinase 3-antineutrophil cytoplasmic antibody antigen binding activity

Objective. To evaluate the potential of a monoclonal proteinase 3- antineutrophil cytoplasmic antibody (PR3-ANCA) antiidiotype autoantibody (5/7 anti-Id) as a candidate for specific immunotherapy in Wegener's granulomatosis (WG), and to estimate the immunodiagnostic value of the corresponding idiotype (5/7 Id). Methods. We analyzed the incidence of 5/7 Id in patients with ANCA-associated vasculitides (WG, microscopic polyangiitis, Churg-Strauss syndrome), in disease controls (systemic lupus erythematosus patients), and in healthy donors. We then investigated the presence of 5/7 Id in relation to disease stage, clinical activity, and organ manifestations in 86 patients with WG. Finally, we investigated the ability of the 5/7 anti-Id reagent to inhibit the binding of PR3-ANCA to corresponding antigen in 19 WG patients. Results. The incidence of 5/7 Id was significantly more frequent in WG patients (43 of 86; 50%). We did not find a significant correlation between the prevalence of idiotype expression and disease activity or organ manifestations. Further, we demonstrated in vitro suppression of PR3-ANCA antigen binding activity by 5/7 anti-Id in 11 of 19 WG patients who were positive for 5/7 Id. Conclusion. This study shows that 5/7 Id is a common idiotype with a significantly increased incidence in WG and that 5/7 anti-Id inhibits PR3-ANCA antigen binding activity. Based on these observations, we conclude that 5/7 anti-Id is a promising tool for the development of a specific immunotherapy for WG.