Are ANA and ANCA the Same?
No, ANA (Antinuclear Antibodies) and ANCA (Antineutrophil Cytoplasmic Antibodies) are completely different autoantibodies that target distinct cellular components and are associated with different autoimmune diseases. 1
Fundamental Differences
Target Antigens and Detection Methods
ANA targets nuclear components of cells, including DNA, histones, and nuclear proteins, detected by indirect immunofluorescence on HEp-2 cells showing nuclear staining patterns (homogeneous, speckled, nucleolar, or centromere). 1, 2
ANCA targets cytoplasmic components of neutrophils and monocytes, primarily proteinase-3 (PR3) and myeloperoxidase (MPO), detected by indirect immunofluorescence on neutrophils showing either cytoplasmic (c-ANCA) or perinuclear (p-ANCA) patterns. 1
Associated Disease Profiles
ANA is the primary screening test for systemic autoimmune rheumatic diseases including systemic lupus erythematosus (SLE), Sjögren's syndrome, systemic sclerosis, and mixed connective tissue disease, with 75-95% positivity in autoimmune hepatitis type 1. 1, 2
ANCA is primarily associated with small vessel vasculitides including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), with c-ANCA/PR3 present in 80-90% of GPA and p-ANCA/MPO in 35% of EGPA. 1, 2
Critical Clinical Distinctions
Autoimmune Hepatitis Context
In autoimmune hepatitis type 1, ANA is detected in 75-95% of patients and serves as a primary diagnostic marker alongside smooth muscle antibodies (SMA). 1
Atypical p-ANCA can be found in 50-96% of autoimmune hepatitis type 1 patients, but these differ from classical p-ANCA by retaining perinuclear staining on formaldehyde-fixed cells and may actually target nuclear membrane components (more appropriately termed p-ANNA). 1
ANCA typically does not coexist with anti-LKM1 antibodies in autoimmune hepatitis type 2, and atypical p-ANCA in autoimmune hepatitis lacks the MPO specificity seen in vasculitis. 1
Testing Algorithm Implications
When evaluating suspected autoimmune hepatitis, test ANA and SMA first in adults, then proceed to anti-LKM1 if these are negative; atypical p-ANCA testing is reserved for seronegative cases where ANA, SMA, anti-LKM1, and anti-SLA are all negative. 1
When evaluating suspected vasculitis, order antigen-specific ELISA for both PR3-ANCA and MPO-ANCA simultaneously, followed by confirmatory indirect immunofluorescence if positive. 1, 2
Important Caveats
Potential for Interference
ANA can cause false-positive c-ANCA results on indirect immunofluorescence, particularly when ANA shows homogeneous nuclear pattern with high titers; this interference should be suspected when c-ANCA is positive but MPO/PR3 ELISA is negative. 3
In drug-induced autoimmune syndromes (particularly hydralazine-associated vasculitis), patients may be simultaneously positive for both ANA and ANCA with high titers, along with anti-histone and anti-MPO antibodies, representing an overlap syndrome rather than equivalence of the antibodies. 4
Diagnostic Specificity
Atypical p-ANCA in autoimmune hepatitis has different clinical significance than classical p-ANCA in vasculitis; the former is associated with liver disease and inflammatory bowel disease, while the latter indicates systemic vasculitis with renal and pulmonary involvement. 1
P-ANCA positivity in systemic autoimmune diseases other than vasculitis (occurring in 62.3% at high titers) rarely shows MPO specificity, indicating these antibodies target unknown autoantigens distinct from vasculitis-associated ANCA. 5