Anatomic Pathology: Vascular Pathology

• Two types of ANCA assays are currently in wide use: IIA and ELISA. IIA is more sensitive, and ELISA is more specific. The optimal approach to clinical testing for ANCA is to screen with IIA and to confirm all positive results with ELISA directed against the specific target antigens (i.e., PR3 and MPO). Both PR3 and MPO are located in the azurophilic granules of neutrophils and the peroxidase-positive lysosomes of monocytes. Antibodies with target specificities for PR3 and MPO are called c-ANCA and p-ANCA, respectively.

• Approximately 90% of patients with active, generalized forms of a necrotizing small vessel vasculitis not caused by the deposition of immune complex deposits (i.e., granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, or microscopic polyangiitis) are ANCA positive (either c-ANCA or p-ANCA).

• The observed titers can vary considerably. Generally, approximately 10% of patients with a necrotizing small vessel vasculitis not caused by the deposition of immune complex deposits are ANCA negative. In patients presenting with limited forms of a necrotizing vasculitis (i.e., patients with only upper respiratory tract disease and no renal involvement), ANCA titers may be within normal limits in 40% of cases.

• ANCA status can change over time—a patient who is ANCA negative on presentation may become ANCA positive with the development of a more generalized disease process.

• A negative ANCA assay does not rule out a vasculitis.