The ANCA Screen with Reflex to Titer is a blood test designed to detect antineutrophil cytoplasmic antibodies (ANCAs). ANCAs are a special type of autoantibody, meaning they are produced by the immune system but mistakenly target the body’s own cells rather than foreign invaders like bacteria. Specifically, ANCAs attack proteins inside neutrophils, a type of white blood cell that plays a major role in fighting infections.
Normally, neutrophils help defend the body by engulfing and destroying pathogens. They contain small sacs, called granules, filled with powerful enzymes that break down bacteria and other threats. In some autoimmune diseases, however, the immune system loses its ability to tell “self” from “non-self” and creates ANCAs against proteins inside these granules—mainly proteinase 3 (PR3) and myeloperoxidase (MPO).
The test starts with a screening phase, using a method called immunofluorescence, where scientists look for specific fluorescent patterns inside neutrophils. If the screen is positive, a reflex to more specific tests is performed: measuring the titer (the concentration) of C-ANCA (usually targeting PR3) and P-ANCA (usually targeting MPO), and sometimes atypical P-ANCA.
The C-ANCA pattern (cytoplasmic) typically lights up the entire cytoplasm and is most closely associated with granulomatosis with polyangiitis (GPA), formerly called Wegener’s granulomatosis. The P-ANCA pattern (perinuclear) mainly surrounds the cell nucleus and is linked to diseases like microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome.
Higher titers of ANCAs strongly suggest active disease, and monitoring these levels can help track disease activity or relapse. However, it is important to know that positive ANCA results are not exclusively found in vasculitis. They can also appear in inflammatory bowel diseases like Crohn’s disease and ulcerative colitis, in autoimmune liver diseases such as primary sclerosing cholangitis, and even in drug-induced lupus or systemic lupus erythematosus (SLE). Importantly, some people with these conditions show a positive ANCA but are not attacking PR3 or MPO, reflecting atypical ANCA patterns.
In rare cases, certain medications can trigger an ANCA-positive vasculitis. Drugs like hydralazine, propylthiouracil, and cocaine contaminated with levamisole can provoke the production of MPO-ANCAs, leading to rapidly progressive kidney disease or lung involvement.
Test results are interpreted against standard reference ranges:
However, a positive test always needs to be interpreted in the context of your symptoms and other laboratory findings. A positive ANCA without signs of vasculitis may not require treatment but instead close observation.
