Vasculitis

Clinical information

ANCA often occur in autoimmune vasculitides of the small blood vessels – especially in granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) which are collectively referred to as ANCA-associated vasculitides (AAV) according to the classification system of the Chapel Hill Consensus Conference. The most important target antigens of the vasculitis-associated ANCA are proteinase 3 (PR3) and myeloperoxidase (MPO). Antibodies against PR3 are most frequently found in patients with GPA (up to 90%), while MPO ANCA have been found in MPA (40% – 80%) and EGPA (20% – 70%). Another form of vasculitis of the small blood vessels is anti-GBM disease (Goodpasture syndrome), which affects the glomerular and, in some cases, also the pulmonary capillaries. Characteristic autoantibodies are directed against the glomerular basement membrane (GBM). Up to 35% of anti-GBM positive samples are also ANCA positive. Due to clinical overlap of AAV and anti-GBM disease, it is recommended to investigate both anti-GBM and ANCA in patients with corresponding kidney damage.

Diagnostics

AAV diagnostics relies predominantly on the monospecific detection of antibodies against proteinase 3 (PR3) and myeloperoxidase (MPO), as well as the detection of ANCA using IIFT. According to the international consensus of 2017, the use of high-quality monospecific assays is particularly recommended for the detection of PR3 and MPO in the context of GPA, MPA and EGPA diagnostics.

With the innovative Anti-PR3-hn-hr ELISA, consisting of a mixture of human native (hn) and human recombinant (hr) PR3, as well as the Anti-MPO ELISA with highly purified human MPO, EUROIMMUN offers high-quality test systems for the detection of AAV. Especially the Anti-PR3-hn-hr ELISA is characterised by a very good specificity (99%) and a significantly higher sensitivity (94%) compared to ELISAs using native antigens (88% and 78%, respectively).

EUROIMMUN offers BIOCHIPs consisting of ethanol (EOH)- and formaldehyde (HCHO)-fixed human granulocytes, which represent the standard for IIFT diagnostics. Further EUROIMMUN-exclusive BIOCHIPs, e.g. HEp-2 cells with sedimented granulocytes, further increase the diagnostic certainty. The EUROPLUS technique allows the combination of conventional cell culture substrates with defined, purified single antigens (PR3, MPO, GBM) on one test field. This considerably simplifies the interpretation of the immunofluorescence patterns.

By means of IIFT, two ANCA types can be displayed: One is the cytoplasmic type (cANCA), which is associated with GPA and is almost always directed against PR3, and the other is the perinuclear type (pANCA), which indicates a spectrum of different diseases. The main target antigen of pANCA is mainly MPO in MPA and EGPA. In addition, there are atypical ANCA (also x-ANCA or DNA-ANCA), which are particularly associated with chronic inflammatory bowel diseases (CIBD) and liver diseases (primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC)). Prominent representatives of these ANCA include those directed against DNA-linked lactoferrin, cathepsin G, lysozyme or BPI. Positive IIFT results should always be interpreted in combination with a monospecific anti-PR3 and anti-MPO test (e.g. ChLIA or ELISA). Since not all cANCA and pANCA are positive in the monospecific test, only a combination of IIFT and ChLIA/ELISA achieves high specificity and sensitivity for ANCA detection.
EUROIMMUN offers ELISA, EUROLINE, ChLIA and IIFT test systems for the detection of ANCA and antibodies against PR3, MPO and GBM.

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ANCA-associated vasculitides