ANCAnegative

ANCAnegative refers to individuals who lack detectable antiproteinase 3 (PR3) or myeloperoxidase (MPO) antibodies despite clinical suspicion for ANCA-associated vasculitis (AAV). ANCA stands for antineutrophil cytoplasmic antibodies. In AAV, most patients test positive for ANCAs, but a minority are ANCA-negative. ANCA testing typically uses indirect immunofluorescence to detect c-ANCA or p-ANCA patterns and antigen-specific immunoassays for PR3-ANCA and MPO-ANCA. In ANCA-negative cases, both IIF and antigen assays may be negative, though some patients later seroconvert or become detectable with highly sensitive methods.

Clinical presentation overlaps with AAV: rapidly progressive small-vessel vasculitis affecting kidneys (pauci-immune focal segmental glomerulonephritis), lungs (hemorrhage or nodules), upper airways, nerves, and skin. ANCA-negative disease can be indistinguishable from ANCA-positive disease based on symptoms alone; organ-damage may be similar, though some cohorts report differing organ involvement or prognosis.

Diagnosis relies on a combination of clinical features, histopathology when feasible (e.g., pauci-immune crescentic GN on renal biopsy), and serology. In ANCA-negative patients, biopsy findings and imaging may guide diagnosis. Differential diagnosis includes other vasculitides, immune complex vasculitis, granulomatosis with polyangiitis with overlap features, and non-vasculitic processes such as infection or malignancy.

Management generally follows AAV principles: induction therapy with glucocorticoids plus an immunosuppressive agent such as cyclophosphamide or rituximab, followed by maintenance therapy (e.g., azathioprine, methotrexate, or rituximab). Treatment is individualized based on organ involvement, disease severity, and patient factors. Purposes of monitoring include renal function, urinary sediment, imaging as needed, and clinical relapse surveillance. The ANCA status itself does not dictate unequivocal prognosis or management, though it may inform risk assessment in some cohorts.