Antinuclear Antibodies

Molecular mechanisms

The antinuclear antibodies may bind to double-stranded DNA (anti-dsDNA), and studies suggest the antibodies are formed during the incomplete removal of cellular material during apoptosis. Additionally, anti-Sm antibodies bind to the Smith protein, a protein contained within small nuclear ribonucleoprotein (snRNP) particles. Scl-70 antibodies interfere with DNA replication by binding to Topoisomerase I, and anti-centromere antibodies affect cell division by binding to centromeres during interphase. Antibodies to Jo-1 prevent histidine binding to tRNA during protein synthesis by targeting histidyl-tRNA synthetase. Additionally, antibodies may target the Ro/SSA antigen, an amino acid sequence that binds to double-stranded and single-stranded DNA. The suspected mechanism is that they may bind to viral DNA of the Epstein Barr virus (EBV) with molecular mimicry, later causing autoimmune disease. Unlike Ro, La/SSB is a protein found primarily in the nucleus. But similar to Ro, La is also known to bind to nuclear material from EBV.

Clinical Significance

• Systemic Lupus Erythematosus (SLE)
  Immunologic criteria for a definitive diagnosis of SLE include abnormal ANA titers in the absence of drugs and the presence of anti-dsDNA or anti-Sm antibodies. Anti-dsDNA antibodies are pathogenic to tissue and organ damage in SLE.
• Scleroderma
  Scleroderma, or systemic sclerosis, involves progressive fibrosis of the skin and organs. The diagnostic basis is a combination of clinical symptoms and increased ANA titers. Scl-70 is highly correlated with scleroderma, while anti-centromere antibodies are moderately correlated.
• Myositis
  Polymyositis (PM) and dermatomyositis (DM) are a group of inflammatory disorders that primarily affect the proximal muscles and cause inflammation. General ANA testing is used to diagnose PM and DM, while anti-Jo1 antibodies are associated with 30% of patients with PM/DM.
• Sjogren's
  Sjogren's syndrome is a chronic autoimmune pathology that destroys the exocrine glands, including the lacrimal and salivary glands. When there is a suspicion of Sjogren's syndrome, testing for anti-Ro/SSA and anti-La/SSB titers is the protocol.
• Psoriatic Arthritis
  Study has found that in PA patients ANA positivity was significantly higher than in age-and sex-matched groups of healthy controls and uncomplicated psoriasis. ANA were more common in Symmetrical Polyarthritis and Arthritis Mutilans than in Asymmetrical Oligoarthritis and Spondarthritis and 'Classical' PA.