The disease

Pathophysiology

The inner ear is meant to be off-limits to the immune system. AIED is what happens when that privilege fails and the labyrinth is treated as foreign.

The immune-privileged inner ear

The cochlea and vestibular labyrinth are normally protected by the blood–labyrinth barrier, which — like the blood–brain barrier — excludes immune cells and large molecules and maintains the homeostasis that delicate mechano-electrical transduction requires.1 Under pathological conditions the barrier breaks down, letting immune components into the endolymphatic and perilymphatic spaces and triggering an immune attack on inner-ear antigens — inflammation, structural damage, and dysfunction of both hearing and balance.

Candidate autoantigens

Several inner-ear proteins have been proposed as targets of the autoimmune response. None has become a validated routine test, but they frame the disease mechanism:

  • 68-kDa protein (HSP-70) — The original Moscicki marker; correlates with steroid response but never standardised — investigational.
  • Cochlin — Major non-collagenous matrix protein of cochlea and vestibule; anti-cochlin antibodies reported in some patients.
  • Type II collagen — Otic-capsule and cartilage antigen, implicated especially in relapsing polychondritis.
  • β-tectorin — Tectorial-membrane component; an emerging candidate autoantigen.

The best known is the 68-kDa protein, thought to correspond to heat-shock protein 70; antibodies against it were the original serological marker described by Moscicki and correlated with disease activity and steroid response, though later studies were inconsistent.2 Anti-cochlin antibodies have likewise been reported in immune-mediated hearing loss but remain investigational.3

Four mechanisms of injury

Once the barrier is breached, several immune pathways converge on the sensory epithelium, stria vascularis and neural elements.4

  1. 1

    Autoantibodies

    Antibodies against inner-ear antigens — the 68-kDa protein (thought to be HSP-70), cochlin, and type II collagen — bind cochlear and vestibular tissue.

  2. 2

    T-cell–mediated cytotoxicity

    CD4+ T-helper cells infiltrate the endolymphatic sac and release TNF-α, IL-1β and IFN-γ, activating macrophages and cytotoxic T cells that destroy hair cells and spiral ganglion neurons.

  3. 3

    Immune-complex deposition

    Circulating immune complexes lodge in the stria vascularis microvasculature, causing capillary obstruction, hypoxia and barrier breakdown — prominent in SLE.

  4. 4

    Complement activation

    Once the barrier is breached, classical/alternative complement pathways form membrane-attack complexes (C5b-9) that lyse cochlear and vestibular cells.

Four mechanisms — autoantibodies, T-cell cytotoxicity, immune-complex deposition and complement activation — converge to destroy hair cells, supporting cells and spiral-ganglion neurons. Their relative mix varies between patients, which helps explain the heterogeneous presentation and treatment response.

Immune-complex deposition and complement-mediated injury are especially prominent where AIED accompanies a systemic disease such as lupus, where immune-complex vasculitis and complement activation are recognised features.5 The variable mix of these mechanisms between patients helps explain the heterogeneity of presentation and of treatment response.

Key points

  • The inner ear is immune-privileged via the blood–labyrinth barrier; AIED follows its breakdown.
  • Candidate autoantigens include the 68-kDa protein (HSP-70), cochlin and type II collagen — none is a validated routine test.
  • Injury is mediated by autoantibodies, T-cell cytotoxicity, immune-complex deposition and complement.
  • The mechanism mix varies between patients, explaining heterogeneous presentation and response.