Utility of autoantibodies for rheumatological diseases
The presence of autoantibodies may indicate autoimmunity in a person with suspected rheumatological disease. Generally, assays for autoantibodies are sensitive but not specific for rheumatological diseases. The diagnostic value of a positive assay depends on the pretest probability for a particular disease.
Antinuclear antibody (ANA) testing can support a diagnosis of systemic lupus erythematosus (SLE) and other inflammatory connective tissue diseases (in particular, systemic sclerosis, Sjögren syndrome, rheumatoid arthritis, and dermatomyositis in adults)Nashi, 2021. However, a positive ANA only supports a diagnosis in people with symptoms and signs of a particular disease (ie a high pretest probability); see When to test for antinuclear antibodies (ANA) for key points on when to test for ANA. Only request an ANA assay if SLE or another inflammatory connective tissue disease is suspectedAustralian Rheumatology Association (ARA), 2018.
A positive ANA, particularly in low titre, can occur in a healthy individual (in up to 25%Nashi, 2021) and a negative ANA does not exclude an autoimmune disease (although SLE would be unlikely)Nashi, 2021. Further testing for other specific autoantibodies should be guided by the result of the ANA titre (ie investigations involve a two-step process); see Significance of antinuclear antibody tests for a detailed discussion.
Rheumatoid factor (RF) is present in approximately 70% of people with established rheumatoid arthritis (RA). It is also present in approximately 5 to 10% of healthy people but is of low specificity, frequently being present in:Ingegnoli, 2013
- inflammatory connective tissue diseases—especially Sjögren syndrome and mixed connective tissue disease
- chronic infection—especially in chronic hepatitis C associated with cryoglobulinaemia
- other diseases—especially primary biliary cirrhosis, malignancy, and sarcoidosis.
Antibodies to cyclic citrullinated peptides (CCP) are more specific markers of RA than RF but are less sensitive. They may be present early, sometimes years before the disease manifests and are associated with poorer outcomesDeane, 2021Kelmenson, 2020.
Antineutrophil cytoplasmic antibodies (ANCA) are found in some of the systemic vasculitides, notably the ANCA-associated small-vessel vasculitides. Only perform testing for ANCAs if the person’s clinical presentation suggests a specific vasculitic syndrome and serological confirmation is required. Initial screening by immunofluorescence can be nonspecific. Cytoplasmic staining ANCA (cANCA) is typically associated with granulomatosis with polyangiitis and peripheral staining ANCA (pANCA) with microscopic polyangiitis.