Can ANA Be Negative in Vasculitis?
Yes, ANA is typically negative in ANCA-associated vasculitis (AAV), and a negative ANA actually helps exclude other autoimmune conditions like systemic lupus erythematosus when evaluating for vasculitis. 1
ANCA Status in Vasculitis
ANCA-Negative Disease is Common
Approximately 10% of patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are persistently ANCA-negative, yet they still have biopsy-proven vasculitis and are treated identically to ANCA-positive patients. 2
In eosinophilic granulomatosis with polyangiitis (EGPA), 60-70% of patients are ANCA-negative at diagnosis, making ANCA negativity the majority phenotype in this vasculitis subtype. 2
ANCA negativity does not exclude a diagnosis of AAV, particularly in patients with disease limited to the respiratory tract or renal-limited vasculitis. 2
Clinical Implications by Disease Subtype
For GPA and MPA:
- ANCA is detectable in approximately 90% of patients with small-vessel vasculitis or necrotizing crescentic glomerulonephritis. 2
- PR3-ANCA is found in 80-90% of GPA patients with active systemic disease. 1, 3
- MPO-ANCA is detected in 75-97% of MPA patients. 2
For EGPA:
- Only 30-40% of EGPA patients are ANCA-positive (predominantly MPO-ANCA). 2
- ANCA-negative EGPA patients more frequently manifest cardiomyopathy and lung involvement, while ANCA-positive patients show more vasculitis features like glomerulonephritis, neuropathy, and purpura. 2
- ANCA-positive and ANCA-negative EGPA are genetically distinct syndromes. 2
ANA Testing in Vasculitis Context
ANA is Generally Negative in AAV
A negative ANA test helps exclude systemic lupus erythematosus and other connective tissue diseases when evaluating suspected vasculitis, as recommended by the American College of Rheumatology. 1
When considering ANCA-negative patients, several non-vasculitic diseases may mimic small-vessel vasculitis, including systemic lupus erythematosus (which would be ANA-positive), infections, and malignancies. 2
Important Caveat: ANA Can Interfere with ANCA Testing
ANA positivity can cause false-positive C-ANCA results when using indirect immunofluorescence, particularly in patients with systemic lupus erythematosus who have positive anti-dsDNA antibodies. 4
This interference underscores why high-quality antigen-specific immunoassays for PR3-ANCA and MPO-ANCA are the preferred screening method, rather than relying solely on immunofluorescence patterns. 2
Diagnostic Approach When ANCA is Negative
If clinical suspicion for AAV remains high despite negative ANCA:
- Perform a second test using either another immunoassay and/or indirect immunofluorescence. 2
- Proceed with tissue biopsy (kidney, lung, or other affected organ) as the gold standard for diagnosis. 2
- In GPA, kidney biopsy has a diagnostic yield as high as 91.5%. 2
Treatment should not be delayed in patients with clinical presentation compatible with small-vessel vasculitis, even if ANCA is negative, particularly in rapidly deteriorating patients. 2
Overlap Syndromes
- Approximately 11% of AAV patients have concomitant autoimmune diseases, most commonly rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis. 5
- In these overlap cases, both ANCA and other autoantibodies (including ANA) may be positive, though this represents a minority of AAV patients. 5