ANCA and Rheumatoid Factor in Granulomatosis with Polyangiitis (Wegener's)
ANCA is typically positive (80-90% of cases), while rheumatoid factor is rarely positive and not a characteristic feature of Wegener's granulomatosis.
ANCA Testing
PR3-ANCA (c-ANCA) is positive in 80-90% of generalized GPA cases and is highly specific for this diagnosis, making it the primary serologic marker 1.
ANCA positivity is found in only approximately 50% of patients with localized Wegener's granulomatosis (disease restricted to the respiratory tract), but rises to 95% in generalized disease 2.
ANCA-negative GPA exists but is uncommon, presenting diagnostic challenges that require reliance on clinical features and histopathology 3.
The anti-PR3 (antiproteinase-3 or C-ANCA) antibody is the specific ANCA subtype associated with Wegener's granulomatosis 4.
Rheumatoid Factor Status
Rheumatoid factor is NOT typically positive in Wegener's granulomatosis and is not part of the diagnostic criteria 4.
When vasculitis occurs (including Wegener's), ANA, ANCA, cryoglobulin, and RF are rarely positive 4.
RF positivity in the context of suspected Wegener's should prompt consideration of coexisting rheumatoid arthritis, which is rare but documented—all 6 reported cases of coexisting RA and WG had positive RF (100%), but this reflected their underlying RA, not the Wegener's 5.
In isolated case reports, RF has occasionally been elevated and tracked with disease activity, but this is exceptional rather than typical 6.
Clinical Implications
The diagnostic workup for suspected Wegener's should include ANCA testing (specifically PR3-ANCA), but RF testing is not routinely indicated unless there are clinical features suggesting coexisting rheumatoid arthritis 4, 1.
A negative ANA test helps exclude other autoimmune conditions like systemic lupus erythematosus when evaluating for vasculitis 1.
Histopathological confirmation remains essential, particularly in ANCA-negative cases, demonstrating necrotizing vasculitis of small arteries, granulomatous inflammation, and geographic necrosis 1.