Anti-Nuclear Antibodies (ANA’s)

ANA’s are autoantibodies that bind to antigens within the cell nucleus.  These are helpful for the diagnosis of rheumatic diseases BUT can be found in patients with non-rheumatic diseases such as liver disease, thyroid disease, chronic infections and malignancies.  Of note, they can also be found at low levels in healthy people.  Positive ANA’s can also predate the development of clinical disease by many years.  ANA results must therefore be interpreted according to the clinical context.

There are two main methods for detecting ANA’s

Indirect Immunofluorescence (IFA)

  • ≤ 1:80 titres is equivocal and non-specific, and can be found in healthy people.
  • ≥ 1:160 titres should prompt further evaluation, but are not necessarily indicative of the presence of disease.
  • The IFA pattern may suggest a specific autoantigen, but are often not diagnostically useful.

BioPlex Assay (immunoassay utilizing bead technology)

  • Measures 13 specific autoantibodies: DNA, Chromatin, Riboprotein, SS-A52, SS-A60, SS-B, Centromere-B, Sm, SmRNP, RNP-68, RNP-A, Scl-70, Jo-1
  • This is increasingly used as first line screen for ANA (cost, efficiency).  It has comparable specificity to IFA testing, but sensitivity for systemic rheumatic diseases is reduced.

Some disease associations

 

Antigen specificityClinical AssociationSensitivitySpecificity
dsDNASystemic Lupus Erythematosus (SLE)70%95%
Ro/SS-ASjogren’s (SjS), SLE8-70% (SjS)

40% (SLE)

87% (SjS)

Moderate (SLE)

La/SS-BSjogren’s (SjS), SLE14-60% (SjS)

Low (SLE)

94% (SjS)

Low (SLE)

SmSLE30%High
Scl-70 (Topoisomerase I)Diffuse Scleroderma10-30%High
RNPSLE,

Mixed Connective Tissue Disease

45% (SLE)High (SLE)