Antinuclear Antibodies Test Summary
Immune system dysregulation can lead to autoantibodies directed against a
variety of intracellular antigens, such as chromatin (dsDNA and histones),
nuclear/nucleolar proteins, centromeres, RNA, cytoplasmic organelles, and
cell membrane components.1,2 These “antinuclear antibodies” (ANA) are often
present in patients with autoimmune (rheumatic) diseases and their detection
can aid in diagnosis of suspected cases.
The ANA test is performed by indirect immunofluorescence assay (IIFA) using
HEp-2 (human epithelial cancer) cells; the “gold standard” method with high
sensitivity to detect ANA present in serum.2,3 The specific staining pattern and
titer of antibody binding, in conjunction with patient clinical symptoms, helps in
differential diagnosis of autoimmune diseases such as systemic lupus
erythematosus (SLE), Sjödren’s syndrome, scleroderma (systemic sclerosis),
mixed connective tissue disease (CTD), rheumatoid arthritis, and
An extractable nuclear antigen (ENA) panel may be used as follow up to a
positive ANA test to identify the particular cellular component that is causing
immunoreactivity and establish the correct diagnosis.1,2,3
Clinical Utility & Indications
As many of the early symptoms of autoimmune CTD (e.g., disabling fatigue,
joint pain, Raynaud’s phenomenon, immune thrombocytopenia, skin rash,
myositis, fever, neurologic signs) are common to other chronic diseases,
detection and quantification of ANA can provide pivotal diagnostic information: 5,6
- confirming a suspected autoimmune CTD
- excluding CTD in patients with ambiguous clinical findings
- differential diagnosis of patients with clinical symptoms suggestive of
- monitoring disease activity (ANA appearance/disappearance; titers do not
correlate with symptom severity)
Conditions most often associated with a positive ANA test 1,2,6,7
- SLE: ~ 75-95% positive for ANA; a negative result makes SLE unlikely
- Drug-induced lupus: can be caused by hydralazine, procainamide,
phenytoin, amiodarone, topiramate, and other medications
- Sjögren syndrome (SS): 40-70% are positive for ANA; a negative result
does not rule out SS
- Scleroderma (systemic sclerosis): 60-90% positive for ANA
- Mixed CTD
- Rheumatoid arthritis
- Autoimmune liver diseases: e.g., autoimmune hepatitis, primary biliary cirrhosis
Positive ANA results include a description of the particular type of fluorescent
pattern seen. Different patterns have been associated with different
autoimmune disorders, with some overlap.2,3,7,8 The dense-fine speckled
pattern in isolation may distinguish ANA-positive “healthy” persons from those
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting up to 1% of us as we age.1 It is characterized by chronic inflammation of the joints and progressive destruction of bones and cartilage. Stiff, painful, and swollen joints can significantly impair quality of life. Early diagnosis and treatment is important.
Diagnosis of RA is based primarily on clinical signs and symptoms and the presence of specific autoantibodies in the blood. Detection of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (CCP) antibodies can confirm clinical diagnosis and help in predicting risk of disease development and gauging severity.2,3
Rheumatoid Factor: RF is an autoantibody against the conserved (Fc) portion of immunoglobulin G (IgG). Although it is a widely used serological marker for the diagnosis of RA and present in 60-90% of patients with established RA, RF is only present in about 50% of patients with early-stage RA and it can be detected in patients with other rheumatic disorders.3 RF can also be detected in 5% of healthy individuals, and in 10-30% of the elderly.2
Anti-Cyclic Citrullinated Peptide (CCP) Antibodies: Postranslational modification of the amino acid arginine to citrulline occurs naturally in the body, marking proteins for degradation during cell growth and turnover. While most people can readily clear the citrullinated proteins, those genetically predisposed to RA cannot, leading to the production of autoantibodies and inflammation.2,4 Anti-CCP is a highly specific early marker for RA and a powerful predictor of disease course.2,4,5 Positive anti-CCP results can confirm a diagnosis of RA, especially where RF is negative.6 The antigen used in the Salveo DiagnosticsTM anti-CCP test is the newest, most sensitive, 3rd generation CCP3.1 peptide that detects IgA and IgG antibodies.7 This is the only assay approved by the American Food and Drug Administration (FDA) for the early detection of RA.8
Uric Acid: Uric acid is a byproduct of purine nucleotide metabolism. Excess serum uric acid can cause crystals to form in the joints and other tissues. In genetically predisposed individuals, this may lead to inflammation and gout—a painful, chronic form of arthritis. High uric acid levels are also a risk factor for cardiovascular disease.9
The upregulated immune response–inflammation cycle characteristic of autoimmune diseases can cause chronic tissue damage over time. However, early treatment of RA or gout can alleviate inflammation, slow damage to the joints, and improve clinical outcome.
- Rheumatoid Arthritis Facts and Statistics. Rheumatoid Arthritis Support Network. Last Edited: August 3, 2016. https://www.rheumatoidarthritis.org/ra/facts-and-statistics/
- Taylor P, et al. Autoimmune Dis 2011;815038. (8)
- Sun J, et al. Clin Exp Rheumatol 2014;32:11-21.
- Van Venrooij WJ, et al. Ann NY Acad Sci 2008;1143:268-285.
- Jilani AA, et al. Int J Rheumatol 2015;2015;728610.
- Aletaha D, et al. Arthritis Rheum 2010;62:2569-2581.
- Vos I, et al. Clin Rheumatol 2017;36:1487-1492.
- Infantino M, et al. Clin Chim Acta 2014;436:237-242.
- Singh JA. Ann Rheum Dis 74(4):631-634.
Why Gut Health?
Poor gut health is at the heart of many chronic conditions. A healthy gastrointestinal (GI) tract is vital to overall well-being and even survival. A recent explosion of scientific research worldwide, including the Human Microbiome Project (HMP), is providing new insights into the importance of the gut as the “gateway to good health” and giving new meaning to the phrase “you are what you eat.”
Lets Get Started
Want to learn more? Give us a call or send us an email and we will get in touch with you as soon as possible.