BACKGROUND Anti-idiotype antibodies (anti-ids) have a potential role in the immunomodulation of various autoimmune disorders. The immunoregulatory role of anti-idiotypic antibodies in ANCA-associated vasculitis needs to be studied. This study was conducted in clinically and histopathologically diagnosed ANCA-associated vasculitis (AAV) patients. METHODS Anti-ids were tested in 100 AAV patients of which 80 had anti-MPO and 20 had anti-PR3 antibodies at various stages of disease over a period of 2-3 years. The disease activity was estimated by the Birmingham vasculitis activity score (BVAS). The affinity-purified ANCA F(ab')2 fragments were prepared using three each of anti-MPO and anti-PR3 high titer sera and were used as idiotype coats for anti-idiotype antibody detection by ELISA. Positivity was confirmed by fluid phase inhibition ELISA. RESULTS Patients who went into remission showed 53.8% anti-ids to anti-MPO and 52.9% to anti-PR3 with low BVAS values (0-8), whereas in patients with active disease, only 12.5% had anti-ids to anti-MPO and 10% had anti-ids to anti-PR3 with comparatively high BVAS (18-32), while five cases who had relapse (BVAS 18-20) did not have anti-ids to anti-MPO or anti-PR3. An inverse correlation was noted between ANCA and anti-ids (r = -0.901). CONCLUSIONS High prevalence of anti-ids in remission cases and low prevalence in active cases with absence of anti-ids in relapse cases as well as an inverse correlation of ANCA and anti-ids indicate its beneficial effect on the disease process, thus suggesting the dynamic role of anti-idiotype networks in the immunoregulation of AAV.