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Autoantibodies

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Overview

Autoantibodies help in the differential diagnosis of rheumatological diseases. These autoantibodies can broadly be divided into:

  • Anti-nuclear antibodies (ANA) – antibodies against nuclear antigens
  • Anti-neutrophil cytoplasmic antibodies (ANCA) – antibodies against cytoplasmic antigens
  • Extracellular antibodies – antibodies against receptors, channels, or secreted molecules

Sensitivity and specificity

Sensitivity is the ability of a test to correctly identify patients with a disease. Specificity is the ability of a test to correctly identify people without a disease. Their application can be remembered using SNout SPin:

  • Sensitivity – useful rule-out test
  • Specific – useful rule-in test

For example, in systemic lupus erythematosus (SLE), antinuclear antibodies (ANA) are present in nearly all patients with SLE, making it a sensitive test (high sensitivity) and good at ruling SLE out. However, it is not specific (less specificity) as ANA levels may be raised in other rheumatological disorders and do not confirm that a patient has SLE if positive.

Anti-double-stranded DNA (anti-dsDNA) is highly specific for SLE, so if this is negative positive in a patient, the likelihood of having SLE is very high.

Therefore, ANA is useful as a screening tool to rule SLE out. If ANA is positive, then anti-dsDNA tests can be performed to confirm the presence of SLE.

Anti-Nuclear Antibodies

Overview

Anti-nuclear antibodies (ANAs) are autoantibodies against nuclear antigens such as DNA and histones. Elevated ANA is non-specific as it can be elevated in multiple rheumatological diseases and therefore, more specific autoantibodies need testing:

  • Anti-double-stranded DNA (anti-dsDNA) – associated with SLE
  • Anti-Smith (anti-Sm) – associated with SLE
  • Anti-histone – associated with SLE and drug-induced lupus
  • Anti-Ro/Sjögren’s syndrome A (SS-A) – associated with Sjögren’s syndrome and SLE
  • Anti-La/Sjögren’s syndrome B (SS-B) – associated with Sjögren’s syndrome and SLE
    • A helpful way to remember these autoantibodies is Ro and La backwards make ORAL
  • Anti-Scl-70 – associated with diffuse cutaneous systemic sclerosis
  • Anti-centromere- associated with limited cutaneous systemic sclerosis (e.g. CREST syndrome)
  • Anti-Jo-1 – associated with polymyositis
  • Anti-Mi-2 – associated with polymyositis and dermatomyositis

Anti-Neutrophil Cytoplasmic Antibodies

Overview

Anti-neutrophil cytoplasmic antibodies (ANCA) describe autoantibodies against cytoplasmic antigens and tend to be associated with vasculitides:

Extracellular Autoantibodies

These describe autoantibodies against extracellular proteins such as receptors or secreted molecules.

Extracellular autoantibodies implicated in rheumatological diseases are:

  • Rheumatoid factor – associated with rheumatoid arthritis (RA)
    • Non-specific as it can be seen in many other conditions (e.g. SLE and Sjögren’s syndrome)
  • Anti-citrullinated peptide (anti-CCP) – more specific for RA

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