Antinuclear Antibodies (ANA)

Antinuclear antibodies (ANA) are autoantibodies (AAK) against components of the cell nuclei that can be used for the diagnosis of autoimmune diseases, i.e., rheumatic diseases or collagenoses. ANA is the basic parameter within the framework of a step-by-step diagnosis for the clarification of an autoimmune disease. The rheumatic form circle or collagenoses include:

  • Dermatomyositis – disease belonging to the collagenoses, which affects the skin and muscles and is mainly associated with diffuse movement pain.
  • Cryoglobulinemia – chronic recurrent immune complex vasculitides (immune disease of the vessels) characterized by the detection of abnormal cold precipitating serum proteins (cold antibodies).
  • Lupus erythematosus – systemic disease affecting the skin and connective tissue of the vessels, leading to vasculitides (vascular inflammation) of numerous organs such as the heart, kidneys or brain.
  • Mixed connective tissue disease – chronic inflammatory connective tissue disease in which symptoms of different collagenoses (systemic lupus erythematosus, scleroderma, polymyositis, Raynaud’s syndrome) occur.
  • Panarteritis nodosa – necrotizing vasculitis that usually affects medium-sized vessels; in this case, the inflammation involves all wall layers (pan = Greek all; arteri- from artery = arteries; -itis = inflammatory).
  • Polymyositis – is classified as a collagenosis; it is a systemic inflammatory disease of skeletal muscle with perivascular lymphocytic infiltration.
  • Progressive systemic sclerosis (systemic sclerosis) – see scleroderma.
  • Rheumatoid arthritis – chronic inflammatory multisystem disease that usually manifests as synovitis (inflammation of the synovial membrane). It is also called primary chronic polyarthritis (PcP).
  • Sharp syndrome – chronic inflammatory connective tissue disease that includes symptoms of several collagenoses such as lupus erythematosus, scleroderma or polymyositis.
  • Sjögren’s syndrome (group of sicca syndromes) – autoimmune disease from the group of collagenoses that leads to a chronic inflammatory disease of the exocrine glands, most commonly the salivary and lacrimal glands; typical sequelae or complications of sicca syndrome are:
    • Keratoconjunctivitis sicca (dry eye syndrome) due to lack of wetting of the cornea and conjunctiva with tear fluid.
    • Increased susceptibility to caries due to xerostomia (dry mouth) due to reduced salivary secretion.
    • Rhinitis sicca (dry nasal mucous membranes), hoarseness and chronic cough irritation and impaired sexual function due to disruption of mucous gland production of the respiratory tract and genital organs.
  • Scleroderma (sclero = hard, dermia = skin) – rare autoimmune disease associated with hardening of connective tissue of the skin alone or of the skin and internal organs (especially the digestive tract, lungs, heart, and kidneys)

The procedure

Material needed

  • Blood serum

Preparation of the patient

  • Not necessary

Disruptive factors

  • Not known

Normal value

Normal value 1: < 80

Indications

  • Suspicion of diseases of the rheumatic system.
  • Suspicion of collagenosis

Interpretation

Interpretation of lowered values

  • Not relevant to disease

Interpretation of elevated values

  • Genetic burden: relatives of collagenosis patients (10-25%).
  • Age > 65 (10-15 %)
  • Autoimmune diseases:
  • Infections (viral, bacterial).
  • Neoplasms: hepatocellular carcinoma (HCC; primary hepatocellular carcinoma) (about 30%).
  • Collagenoses:
    • “Mixed connective tissue disease” (100%).
    • Systemic lupus erythematosus (SLE) (95-100%).
    • Systemic sclerosis (95%)
    • Sjögren’s syndrome (about 90%)
    • Myositides (about 60%)
  • Rheumatoid arthritis (about 30%) or other diseases from the rheumatoid form circle.
  • Vasculitides (vascular inflammations)
  • Medications:

In (round brackets) data on the frequency of a positive ANA test. Further notes

  • Low ANA titers (1:80 to 1:320) occur frequently even in healthy individuals (up to 30%).
  • Titer level and fluorescence pattern of ANA are important diagnostic criteria.
  • Causes of false-positive ANA titers are drugs (drugs that can induce drug-induced lupus or, in rare cases, SLE; see “Lupus erythematosus/causes”); more commonly, drugs induce ANA without clinical symptoms.
  • Increasing mercury exposure increases the risk for elevated ANA levels.
  • In the case of positive ANA screening (from ANA titers of 1:320 or, if autoimmune disease is suspected, from a titer of 1:80), the following laboratory tests should be performed:
    • DsDNA antibody
    • ENA antibody

    Detection of dsDNA-AAK and ENA-AAK is highly specific for autoimmune disease!

  • If rheumatoid arthritis is suspected, the following additional laboratory tests should be performed:
    • CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
    • Rheumatoid factor (or CCP-AK)
    • HLA-B27 (histocompatibility antigens).
  • A negative ANA test does not completely rule out collagenosis!