Does a positive 68kD HSP70 (heat shock protein 70) antibody test indicate autoimmune inner ear disease?

Does a Positive 68kD HSP70 Antibody Test Indicate Autoimmune Inner Ear Disease?

A positive 68kD HSP70 antibody test alone is not sufficient to diagnose autoimmune inner ear disease (AIED), as it has limited sensitivity (54.5%) and specificity (42.9%) for this condition. 1

Understanding HSP70 Antibodies and AIED

What is AIED?

Autoimmune inner ear disease is characterized by:

• Progressive, often bilateral sensorineural hearing loss
• May include vestibular symptoms (vertigo, dizziness)
• Potential fluctuation in symptoms
• Response to immunosuppressive therapy, particularly corticosteroids

HSP70 Antibody Testing - Limitations

• Low sensitivity: Only 9.4% of patients with sudden deafness, idiopathic progressive sensorineural hearing loss, or Ménière's disease showed anti-HSP70 antibodies in one study 2
• Variable prevalence: 47% of Ménière's disease patients had anti-HSP70 antibodies in another study 3
• Higher prevalence in bilateral disease: 58.8% in bilateral Ménière's disease versus 33.3% in unilateral cases 3
• Poor correlation with treatment response: The HSP70 antibody test has limited clinical utility in diagnosing AIED 1

Clinical Approach to Suspected AIED

Key Diagnostic Indicators

1. Clinical presentation is more important than antibody testing:

   • Progressive bilateral sensorineural hearing loss
   • Fluctuating hearing symptoms
   • Response to corticosteroid therapy

2. Warning signs suggesting non-idiopathic causes:

   • Bilateral sudden hearing loss
   • Antecedent fluctuating hearing loss
   • Concurrent severe vestibular symptoms 4

3. Associated conditions to consider:

   • Ménière's disease
   • Cogan's syndrome (may include eye inflammation)
   • Systemic autoimmune diseases 4

Diagnostic Algorithm

1. Evaluate hearing loss pattern:

   • Progressive and/or fluctuating hearing loss suggests possible autoimmune etiology
   • Bilateral involvement increases suspicion

2. Consider response to steroid trial:

   • Approximately 70% of AIED patients respond to oral prednisone 1
   • Response to immunosuppression is more diagnostic than antibody testing

3. Rule out other causes:

   • MRI to exclude retrocochlear pathology
   • Evaluate for systemic autoimmune conditions (present in ~29% of patients with idiopathic progressive SNHL) 2

Interpreting a Positive HSP70 Result

A positive HSP70 antibody test should be interpreted in the clinical context:

• In isolation: Not diagnostic of AIED
• With typical clinical features: Supports but does not confirm AIED
• With systemic autoimmune disease: May indicate inner ear involvement

Management Implications

If clinical suspicion for AIED exists (regardless of HSP70 status):

1. First-line therapy: Trial of oral corticosteroids

   • Response supports autoimmune etiology
   • Non-response does not rule out AIED

2. For steroid-responsive cases:

   • Consider steroid-sparing immunosuppressants
   • Biologics like adalimumab or rituximab may improve vertigo, tinnitus, and aural fullness (though hearing improvement is less consistent) 1

3. Long-term monitoring:

   • Regular audiometric testing
   • Vigilance for development of systemic autoimmune disease

Clinical Pearls

• The 68kD protein detected in AIED patients is now known to represent HSP70 5
• Western blot using both heat-shocked and non-heat-shocked cells may provide more reliable detection of anti-HSP70 antibodies 5
• Rapid progression to complete hearing loss is uncommon in AIED patients 6
• The clinical course of AIED may be more variable and benign than previously reported 6

In summary, while a positive HSP70 antibody test may suggest an autoimmune component to inner ear disease, it should be considered alongside clinical presentation, response to therapy, and evaluation for systemic autoimmune conditions rather than as a standalone diagnostic marker.