Discovered in 1982, ANCA targets myeloid specific proteins found in the cytoplasm of segmented granulocytic (neutrophilic) white blood cells and monocytes. According to the Tietz Textbook of Clinical Chemistry, blood tests for ANCA and its subtypes are used to help with the diagnosis of a number of different autoimmune disorders. However, because many antigens react in immunofluorescent blood tests for ANCA the test has its limitations.
Subtypes of ANCA
Although early studies suggested that there were three ANCA subtypes, it’s now known that only two subtypes exist: perinuclear (P-ANCA) with a protoplasmic staining pattern; and cytoplasmic (C-ANCA). Test results that show P-ANCA staining variations are sometimes reported as atypical P-ANCA. Tests for ANCA generally include total ANCA, P-ANCA and C-ANCA. Each of the subtypes is associated with a specific cluster of diseases although in some testing methods there may be cross-reactivity with antinuclear antigens (ANA).
Particularly significant, certain subsets of ANCA specifically react with the myeloid proteins PR-3 and myeloperoxidase (MPO) and tend to be specific for vasculitis and glomerulonephritis. Blood tests that specifically target these antigens are considered superior. Blood tests that demonstrate this reactivity should be used on all patients that test positive using other methods for C-ANCA or P-ANCA to assist with disease diagnosis. Other test methods yield numerous false positive results because of the many other antigens that cause insignificant reactions.
Diseases Associated with ANCA
The presence of ANCA is primarily associated with the disorders necrotizing granulomatosis; and pauci-immune necrotizing vasculitis. These disorders target the kidneys as well as many other tissues. Autoimmune disorders that fall into these classifications include Wegener granulomatosis; microscopic necrotizing polyarteritis; systemic vasculitis; Churg-Strauss syndrome; drug-induced vasculitis (associated with methimazole, propylthiouracil and hydralazine); autoimmune hepatitis; and inflammatory bowel disease. Disorders of vasculitis associated with ANCA are called ANCA-associated vasculitides.
P-ANCA are seen in Churg-Strauss syndrome; Kawasaki syndrome; giant-cell arteritis; glomerular membrane basement disease; rapidly progressive glomerulonephritis; polyarteritis nodosa (PAN); inflammatory bowel disease including Crohn’s disease; primary sclerosing cholangitis; rheumatoid arthritis; and drug-induced vasculitis. Non-specific or false positive reactions are most common in immunofluorescent tests for P-ANCA. For this reason about 17 percent of patients, especially younger patients with juvenile arthritis, show the presence of P-ANCA although this is generally considered a false positive reaction. Similarly, the P-ANCA detected in the liver disorders primary sclerosing cholangitis and autoimmune hepatitis have an incomplete (atypical) staining pattern. In some laboratories, where differentiation is made and atypical P-ANCA are reported, this information is helpful in diagnosis.
C-ANCA are seen in microscopic polyarteritis, Wegener granulomatosis, Henoch-Schonlein purpura, Churg-Strauss syndrome, Kawasaki syndrome, polyarteritis nodosa, and glomerular basement membrane disease. C-ANCA are seen in up to 85 percent of patients with Wegener granulomatosis and vasculitis. Although this finding is controversial, some researchers report that levels or titers of C-ANCA parallel disease activity and can be used to evaluate disease progression as well as treatment response. Other researchers feel that results can be misleading and that symptoms are more relevant for evaluating treatment response and disease progression (Schmitt et al.)
Glomerular Diseases Associated with ANCA
Glomerular diseases (glomerulonephritis) are kidney (renal) disorders that affect the blood supply of the renal tubules. This results in the loss of complete functional units called nephrons. This leads to the inability of the kidneys to clear products of protein metabolism, which causes increased levels of blood urea nitrogen (BUN) and a condition known as the uremic syndrome. The most common type of glomerulonephritis is IgA nephropathy in which deposits of the protein immunoglobulin A interfere with kidney function.
Rapidly Progressive Glomerulonephritis (RPGN) is a heterogeneous group of rapidly progressive kidney disorders that can lead to kidney failure in only a few weeks or few months. These syndromes are characterized by focal necrotizing glomerulonephritis and crescent formation within the kidney’s Bowman capsules. An abundance of epithelial cells and white blood cells known as macrophages compress the glomeruli of the kidneys and obstruct the proximal convoluted tubules, which compromises kidney function.
RPGN may be either autoimmune in nature or it may occur as a secondary condition related to infectious disease or as a disease secondary to other conditions, or as an adverse reaction to medications, including rare reactions to anti-thyroid drugs. Anti-glomerular basement membrane (GBM) antibodies may be present and up to 80 percent of patients show the presence of ANCA with or without an accompanying vasculitis.
Sources
- Wilhelm H. Schmitt; Fokko J. van der Woude. 2004.
- “Clinical Applications of Antineutrophil Cytoplasmic Antibody Testing” Medscape News.
- Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 2006. Philadelphia: Elsevier Health Science Center.
Elaine Moore - I'm a retired medical technologist and medical writer with more than 30 years experience working in hospital laboratories. Currently, I ...
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