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Antibodies are proteins generated by the immune system to detect and disarm foreign pathogens. Autoantibodies are antibodies that mistakenly attack the body's own cells and tissues. It’s estimated that up to 15% of healthy people have some circulating autoantibodies, with that percentage increasing with age and during viral illnesses. (Source)

In autoimmune diseases, though, elevated levels of autoantibodies are associated with inflammation, swelling, and tissue damage. (Source, Source, Source) An autoantibody known as the anti-Smith (anti-Sm) antibody is highly specific to systemic lupus erythematosus, or SLE. Approximately 1% of healthy individuals have anti-Smith antibodies, while 20% to 40% of people with SLE have them. (Source, Source)

While there is no clear connection between the level of anti-Sm antibodies in the blood and the severity or prognosis of SLE, a small study published in Annals of the Rheumatic Diseases did find anti-Smith antibody levels associated with disease activity in patients with new-onset SLE, suggesting that monitoring anti-Smith antibody levels over time can help gauge lupus activity. (Source, Source, Source)

Autoantibody Blood Tests for Lupus

Blood tests can be performed to detect different forms of autoantibodies and help clinicians diagnose lupus. However, these tests are not conclusive by themselves and need to be combined with the presence of other physical symptoms to make a diagnosis.

Antinuclear Antibodies

Antinuclear antibodies (ANA) are antibodies that bind to the nucleus — the enclosed cell structure that holds DNA. Ninety-eight percent of people with SLE test positive for antinuclear antibodies.

Testing for Antinuclear Antibodies (ANA)

To test for ANA, the patient’s serum — the part of the blood that is left after red and white blood cells, platelets and clotting factors are removed — is placed on a slide lined with cells, usually from a rodent liver or kidney or a human tissue culture cell line. If antinuclear antibodies are present, the serum will bind to the cells on the slide.

Next, a second antibody treated with a fluorescent dye is introduced. This antibody binds to the ANA and will fluoresce, or glow, when exposed to ultraviolet light. The sample is viewed with a fluorescent microscope to see how many ANA are present and what kind of pattern of fluorescence they create.

Patterns of ANA Fluorescence  

The pattern of the ANA fluorescence provides valuable insights into a patient's condition. 

  • A homogenous or diffuse pattern, where the entire nucleus is fluorescent, is commonly found in people with SLE and mixed connective tissue disease (MCTD). 
  • A peripheral pattern, where the edges of the nucleus are fluorescent, is almost only found in people with SLE. 
  • A speckled pattern of fluorescence on the nucleus is seen with SLE, MCTD, rheumatoid arthritis and other autoimmune diseases.

(Source, Source)

ANA Panel Identifies Specific Autoantibodies

An ANA panel can be performed to identify specific autoantibodies and help narrow down a diagnosis. The ANA panel checks for:

  • Anti-double-stranded DNA antibody (anti-dsDNA), found in approximately 30% of patients with systemic lupus and less than 1% of healthy individuals
  • Anti-Smith antibody, found in 20% to 40% of patients with lupus and less than 1% of healthy individuals; nearly exclusive to lupus and rarely found with other rheumatic diseases
  • Anti-U1RNP, found in approximately 25% of patients with lupus and less than 1% of healthy individuals; also found in rheumatoid arthritis, systemic sclerosis, Sjogren’s syndrome, and polymyositis
  • Anti-Ro/SSA and anti-La/SSB, found in 30% to 40% of patients with systemic lupus and common in people with lupus who test negative for other ANA; also found in other rheumatic diseases, such as rheumatoid arthritis, systemic sclerosis, and polymyositis


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Rheumatoid Arthritis
January 6, 2023

The Anti-Smith Antibody & Its Role in Diagnosing Lupus

Anti-Smith antibody is specific to systemic lupus erythematosus. Research suggests monitoring anti-Smith antibody levels can help measure lupus activity.
Medically Reviwed
Medically Reviewed by
Dr. Anshul Gupta
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