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Autoantibodies

Autoantibodies are immunoglobulins produced in response to self-antigens. 

Rheumatoid Factors (RF) and Anti-cyclic Citrullinated Protein (anti-CCP) Antibodies

  • RF is not a diagnostic test for JIA.
  • RF level can be elevated as an acute phase reactant (for example in infective endocarditis, hypergammaglobulinaemic states and chronic infections) so a result can only be considered positive if the RF is present in high titre (>1:40) on at least two occasions (at least 3 months apart).
  • Less than 5% of children with JIA are RF-positive and the majority of these children will be older girls with a polyarticular disease course.
  • The long-term outlook for children with RF positive polyarticular JIA is guarded; the majority of these children will continue to have polyarticular disease requiring systemic immunosuppression well into adult life.
  • RF can be associated with other rheumatological illnesses of childhood, in particular SLE and the overlap conditions such as mixed connective tissue disease or Sjögren's syndrome.
  • RF is not useful to monitor rheumatological disease activity. 
  • Anti-CCP antibodies occur in a small number of children with RF positive polyarticular JIA.
  • Anti-CCP antibodies are thought to be associated with an increased risk of erosive (and therefore potentially disabling) joint disease.

Antinuclear Antibodies (ANA)

  • ANAs are directed against the nuclear contents of the cell. Titres are usually reported as positive based on local norms and control populations. A titre of 1 in 160 or above is more likely to be significant. A lower titre will often associate with normal healthy children.
  • ANAs are not a useful screening tool for autoimmune disease and results must be interpreted in the context of clinical findings.
  • A positive ANA can be found in up to 15% of healthy children and can occur as a consequence of viral infection, malignancy or IgA deficiency.
  • A persistently positive ANA can be associated with a number of rheumatological conditions including Juvenile Systemic Lupus Erythematosus (JSLE), drug-induced lupus, undifferentiated connective tissue disease, Sjögrens Syndrome, Juvenile Dermatomyositis, Scleroderma and Systemic Sclerosis. 
  • A positive ANA can occur in some children with JIA, most frequently girls with younger age at onset and an oligoarticular disease course. Children with oligoarticular JIA who are ANA positive are at highest risk for chronic anterior uveitis.
  • ANA is not useful for monitoring disease activity.
  • Indirect Immunofluorescence (IIF) is the recommended method of performing ANA testing. ELISA test is unreliable to assess ANA status and is not as informative regarding ANA patterns. The pattern of IIF may point towards the particular subset of connective tissue disorders (e.g., speckled pattern with systemic sclerosis). 

Some autoantibodies are more specific for rheumatic illness and, in particular, connective tissue diseases and vasculitis. These are further discussed in clinical scenarios. For example:

Anti-double Stranded DNA Antibodies (dsDNA)

  • dsDNA autoantibodies are highly specific for SLE and are detected in many (approximately 2/3) of children with lupus nephritis.
  • Titres can correlate with renal disease activity in some children with SLE.
  • Other extractable nuclear antigens (including anti-RNP antibodies, anti-Sm antibodies, anti-Ro and anti-La antibodies) occur with variable frequencies in children with SLE and related connective tissue disorders.
  • These auto-antibodies are detected by ELISA testing. 

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