Anti–Cathepsin G Antibodies

Vasculitides comprise a heterogeneous group of disorders characterised by inflammation and necrosis of the walls of arteries and veins of different calibres supplying various body districts. Symptoms include signs of local and systemic inflammation and secondary symptoms arising from reduced tissue perfusion.

The term “ANCA-associated systemic vasculitides” (AAV), recognised by the Chapel Hill Consensus Conference, identifies primary vasculitides with similar clinical and pathological features in which antibodies to neutrophil cytoplasmic constituents are frequently detected.

AAVs are classified into three main forms, based on clinical phenotype and ANCA subtype:

• Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis)
• Microscopic polyangiitis (MPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg–Strauss syndrome)

ANCA are autoantibodies against antigens located predominantly in the cytoplasmic granules of neutrophils and monocytes.

There are different methods for ANCA detection. Indirect immunofluorescence (IIFT) on neutrophil granulocytes allows identification of the main associated fluorescence patterns:

• cANCA pattern: characterised by a granular fluorescence uniformly distributed throughout the granulocyte cytoplasm, sparing the nucleus. This pattern is mainly linked to antibodies against proteinase 3 (PR3). Atypical cANCA patterns (flat homogeneous cytoplasmic pattern) can be associated with anti-BPI (bactericidal permeability-increasing protein) antibodies, detectable in rare settings such as Pseudomonas infections and subacute bacterial endocarditis.
• pANCA pattern: a predominantly smooth fluorescence localised around the granulocyte nucleus. Myeloperoxidase (MPO) is the principal pANCA antigen in patients with MPA and EGPA. However, pANCA may also occur in a range of other autoimmune and non-autoimmune conditions—such as inflammatory bowel diseases, primary sclerosing cholangitis, autoimmune liver diseases, connective-tissue diseases, rheumatoid arthritis, malignancies, and infections—where ANCAs are almost always directed against neutrophil constituents other than MPO. Additional pANCA target antigens include lactoferrin, elastase, BPI, cathepsin G, lysozyme and β-glucuronidase.