"Clinical UseEvaluate suspected autoimmune rheumatic diseases

Clinical Background

Autoimmune rheumatic diseases are conditions in which the immune system attacks the joints and certain organs. They are often difficult to diagnose, as their symptoms can be vague, vary from patient to patient, and often overlap. Diagnosis is most often based on a compilation of symptoms and signs, including clinical information and laboratory test results. Testing for antibodies associated with different conditions can provide useful information, but no single test provides a definitive diagnosis for any one rheumatic disease. 

Antinuclear antibody testing

Testing for antinuclear antibodies (ANAs) using an immunofluorescence assay (IFA) is an important part of evaluating patients suspected of having certain autoimmune rheumatic diseases. ANAs are a group of autoantibodies directed against diverse nuclear and cytoplasmic antigens. They are associated with several autoimmune rheumatic diseases, but the diagnostic value of ANA testing varies with the specific clinical condition. While ANA test results are positive for most patients with certain conditions, such as mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), or systemic sclerosis, such results may be positive or negative for patients with other common autoimmune conditions, such as Sjögren syndrome or rheumatoid arthritis (RA). Thus, a positive ANA result alone is not sufficient for diagnosis, and a negative ANA result does not definitively rule out many autoimmune rheumatic conditions.

Knowing the ANA titer and pattern can help interpret positive ANA results. A titer of at least 1:40 is considered positive, although most patients with autoimmune disease will have higher levels. Low-positive titers (eg, 1:40) are not uncommon in healthy individuals (20% to 30%), but using a threshold of 1:40 can increase sensitivity for SLE, systemic sclerosis, and Sjögren syndrome.1,2 For patients with positive ANA screening results, nuclear and cytoplasmic antibody fluorescence patterns may inform the differential diagnosis, but they may not be specific for individual diseases.3,4 For example, a homogeneous nuclear pattern may be associated with SLE, drug-induced SLE/vasculitis, or juvenile idiopathic arthritis, while a diffuse cytoplasmic pattern could be consistent with SLE or an inflammatory myopathy.5

Specific autoantibodies

ANAs are highly prevalent in many autoimmune conditions (Table 1), making ANA testing sensitive but not highly specific; tests for individual antibodies offer greater specificity and are often needed to help establish the diagnosis. The relative importance of testing for ANA versus condition-specific antibodies varies and is often indicated in diagnosis or classification criteria for each condition. "

Includes
If ANA Screen, IFA is positive, then ANA Titer and Pattern will be performed at an additional charge (CPT code(s): 86039).

Methodology
Immunofluorescence Assay (IFA)

Reference Range(s)
ANA Screen    Negative
  ANA Titer     
  <1:40    Negative
  1:40-1:80    Low antibody level
  >1:80    Elevated antibody level

Alternative Name(s)
FANA,Fluorescent ANA,Progressive ANA,Hep-2,Antinuclear Antibody Screen