What is the clinical significance of a positive Antinuclear Antibody (ANA) result with a spindle pattern?

Clinical Significance of a Spindle Pattern Positive ANA

A spindle pattern positive ANA (anti-mitotic spindle apparatus antibodies) is most commonly associated with connective tissue diseases, particularly Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and undifferentiated connective tissue disease, but is not specific to any single autoimmune condition. 1, 2

Understanding Anti-Mitotic Spindle Apparatus (MSA) Antibodies

Anti-MSA antibodies represent an uncommon pattern of antinuclear antibodies that target components of the mitotic spindle apparatus. They are detected through indirect immunofluorescence assay (IIFA), which remains the gold standard for ANA testing 3.

The main types of anti-MSA patterns include:

• Nuclear Mitotic Apparatus (NuMA) pattern (most common, ~56% of MSA patterns)
• MSA-2 pattern (second most common, ~25% of MSA patterns)
• Centrosome pattern
• CENP-F pattern

Clinical Associations

Anti-MSA antibodies have been associated with:

• Connective Tissue Diseases (CTDs) - Present in approximately 45% of patients with anti-NuMA antibodies 2

  • Sjögren's syndrome (18.1%)
  • Rheumatoid arthritis (13.8%)
  • Systemic lupus erythematosus (11%)
  • Undifferentiated connective tissue disease

• Other conditions with potential associations:

  • Chronic idiopathic urticaria (associated with NuMA pattern) 1
  • Sensorineural hearing loss (associated with MSA-2, centrosome, and CENP-F patterns) 1
  • Organ-specific autoimmune diseases (17.5% of patients with NuMA antibodies) 2
  • Malignancies (particularly papillary thyroid cancer) 1

Diagnostic Value and Interpretation

When interpreting a spindle pattern positive ANA:

1. Prevalence: Anti-MSA patterns are uncommon, representing approximately 1% of positive ANA tests 1

2. Specificity: These antibodies often behave as monospecific antibodies (81% of cases have anti-MSA as the only positive ANA test) 1

3. Titer significance: Higher titers of NuMA antibodies may warrant more extensive screening for connective tissue diseases 2

4. Diagnostic algorithm:

   • Confirm the pattern through expert interpretation of IIFA results
   • Consider testing for specific antibodies that may coexist (anti-Ro antibodies are found in 15.5% of anti-MSA positive patients) 1
   • Evaluate for clinical features of connective tissue diseases
   • Consider referral to rheumatology, especially with high titers or symptoms suggestive of CTD

Important Considerations

• Anti-MSA antibodies are not specific for any single autoimmune disease, making clinical correlation essential
• In approximately 37.5% of patients with anti-NuMA antibodies, no autoimmune pathology is documented 2
• The presence of both ANA and HLA-B27 significantly increases the likelihood of spondyloarthropathies and warrants rheumatology referral 4
• Anti-HsEg5 (another type of anti-MSA) does not appear to associate with any specific pathology 2

Pitfalls to Avoid

• Do not over-interpret the significance of a positive anti-MSA pattern without clinical correlation
• Avoid assuming that all positive ANA tests indicate autoimmune disease, as up to 25% of sera from apparently healthy individuals can be ANA positive 3
• Remember that the IIFA technique requires substantial technical expertise, and interpretation should be performed by experienced laboratory personnel

The detection of uncommon ANA patterns like anti-MSA should be encouraged as they may provide valuable diagnostic information in autoimmune and other disease conditions 5.