A relationship among antineutrophil cytoplasmic autoantibodies (ANCA), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and "renal-limited" vasculitis (pauci-immune glomerulonephritis without evidence of extrarenal disease) has been established. ANCA are also present in a substantial subset of patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss, abbreviated as EGPA) and certain drug-induced vasculitis syndromes. ANCA testing plays a critical role in the diagnosis and classification of vasculitides, even as debate about their ultimate importance in the pathogenesis and pathophysiology of these conditions continues. (See 'Introduction' above.)
●Two types of ANCA assays are in wide use: indirect immunofluorescence assay; and enzyme-linked immunosorbent assay (ELISA). In vasculitis, the two relevant target antigens detected by ELISA are proteinase 3 (PR3) and myeloperoxidase (MPO). Specific ELISAs for antibodies to PR3 and MPO are commercially available and should be part of any standardized approach to the testing for ANCA. PR3-ANCA and MPO-ANCA are associated with substantially higher specificities and positive predictive values than the immunofluorescence patterns to which they usually correspond (cytoplasmic [C]- and perinuclear [P]-ANCA, respectively). (See 'Technical issues' above.)
●ANCA are associated with a variety of disorders (see 'Disease associations' above):
•GPA – Approximately 90 percent of patients with active, generalized GPA are ANCA positive. Among patients who have GPA with ANCA, 80 to 90 percent have PR3-ANCA. (See 'Granulomatosis with polyangiitis' above.)
•MPA – Nearly 90 percent of patients with MPA are ANCA positive, and most ANCA-positive patients with MPA have MPO-ANCA. (See 'Microscopic polyangiitis' above.)
•Renal-limited vasculitis – The majority of patients with renal-limited vasculitis are ANCA positive, with 75 to 80 percent having MPO-ANCA. (See 'Renal-limited vasculitis' above.)
•EGPA – ANCA, both PR3 and MPO, have been detected with variable frequencies in patients with EGPA. Among such patients, the vast majority have MPO-ANCA. (See 'Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)' above.)
•Other glomerular disorders – Between 10 and 40 percent of patients with anti-glomerular basement membrane (GBM) autoantibody disease are ANCA positive at the time of diagnosis, and ANCA is usually directed against MPO rather than PR3. In addition to anti-GBM autoantibody disease, ANCA-associated glomerular disease has also been described to coexist with a variety of other disorders including membranous nephropathy, lupus nephritis, IgA nephropathy, and bacterial infection-related glomerulonephritis (mostly poststreptococcal and Staphylococcus associated). (See 'Anti-GBM autoantibody disease' above and 'Other concurrent glomerular diseases' above.)
•Drug-induced ANCA-associated vasculitis – Certain medications may induce forms of vasculitis associated with ANCA (mostly MPO), including hydralazine, propylthiouracil, methimazole, carbimazole, and minocycline. Other drugs, such as allopurinol, penicillamine, procainamide, thiamazole, clozapine, phenytoin, rifampicin, cefotaxime, isoniazid, and indomethacin, have less certain causal associations with ANCA-associated vasculitis. (See 'Drug-induced ANCA-associated vasculitis' above.)
•Other – ANCA may also be seen with nonvasculitic rheumatic disorders, autoimmune gastrointestinal disorders (such as ulcerative colitis), cystic fibrosis, levamisole (which is sometimes a contaminant in cocaine) exposure, and bacteremia and other infections. (See 'Nonvasculitic rheumatic disorders' above and 'Autoimmune gastrointestinal disorders' above and 'Cystic fibrosis' above and 'Cocaine and levamisole' above and 'Bacteremia and other infections' above.)
●The results of ANCA testing must be considered in the clinical context, and the diagnosis of vasculitis or glomerulonephritis often requires a tissue biopsy. A negative ANCA test does not exclude the diagnosis of GPA, MPA, or renal-limited vasculitis, and a positive test does not necessarily establish the diagnosis (unless the clinical presentation is highly suggestive of a vasculitis). In addition, among ANCA-positive patients with GPA or MPA, a rising titer does not definitively indicate increasing disease activity, and a titer that becomes negative does not guarantee disease quiescence. (See 'Clinical applications' above.)
