Immune mediated inner ear disease

From Otolaryngology Online


Inner ear is an extension of central nervous system. Initially these areas were thought to be immunoprivileged sites due to the presence of blood brain / blood labyrinthine barriers. It has now been proved that inner ear and central nervous system is capable of mounting an immune response.

Immune mechanism of inner ear:

In the normal resting state, the inner ear contains immunoglobin and the endolymphatic sac contains immunocompetent cells. Immunoglobin can also cross the blood labyrinthine barrier and is present in perilymph at a level of 1/1000 of concentration found in serum. Concentration of immunoglobin in the perilymph is considerably higher than that of CSF. This has been attributed to the water absorptive properties of endolymphatic sac.

Studies have shown that levels of IgG predominates over IgM and IgA which are also present in low quantities. These immunoglobulins protects the inner ear from pathogens by neutralization, opsonization and complement fixation. Opsonization and complement fixation require the actions of immunocompetent cells in conjunction with immunoglobin. Normal cochlea doesnot contain immunocompetent cells. The endolymphatic sac contains full range of immunocompetent cells ( helper and suppressor classes of T lymphocytes, macrophages, and B cells bearing IgM, IgG and IgA).

Endolymphatic sac lies in close proximity to lymphatics that drain into the jugular chain of nodes. This also supports the immunological role played by the endolymphatic sac. Evidence also shows the presence of phagocytosed antigen within the macrophages of the endolymphatic sac.

Effects of antigen challenge to inner ear:

Direct challenge of perilymph with antigen causes antibody increase in the perilymph. The levels peak within 4-7 weeks, and is not associated with increased vascular permeability. Numerous plasma cells have been noted in the scala tympani and endolymphatic sac during this response. Cellular infiltrates start to occur in close proximity to the sac within the first 48 hours of antigen challenge.

Secretion of antigen specific antibody is the mechanism used by inner ear to protect itself from antigenic insults. This is the reason for a late peak of immunoglobulins (4-7 weeks) after an antigenic insult. This time can be shortened by previous immunization status.

In addition to the endolymphatic sac, the inner ear also receives systemic immune cells for protection against viral and bacterial antigens through other means also. The spiral modiolar vein plays a key role in this secondary immune mechanism. Egress of lymphocytes from circulation into lymph nodes have known to occur via specialized post capillary venules which have a unique morphology. They are also termed as high endothelial venules (HEV). The spiral modiolar vein also undergoes (HEV) like transformation in response to inflammation.

1. Macrophages and granulocytes are observed as early as 6 hours after immunological challenge in the endolymphatic sac and cochlea.

2. Number of T - helper cells gradually increase in the endolymphatic sac peaking at about 2-3 weeks.

3. Increased levels of T - suppressor cells are not detected in the cochlea / endolymphatic sac till about 3 weeks post challenge.

4. IgG cells are seen in the sac as early as day 1 of insult, IgM follows shortly with an increase on day 2, and IgA don't appear until 3 weeks pass after antigenic insult.

The chain of events intended to protect the inner ear against pathogens can lead to sensorineural hearing loss. These patients manifest with degeneration of organ of corti, stria vascularis, and spiral ganglion. There may be also associated mild endolymphatic hydrops. It has also been proved that more robust the immune reaction worse is the hearing loss.

Autoimmune deafness:

In addition to the damage caused by immune response to invading antigens, the inner ear may also be damaged by autoimmune mechanisms. Autoimmunity causes damage to inner ear by:

1. Production of autoantibodies against tissue antigens

2. Deposition of antigen-antibody immune complexes in the tissue

3. Infiltration and destruction of tissue by cytotoxic T cells

Lehnhardt in 1958 suggested that anticochlear antibodies could cause irreversible sensorineural hearing loss. McCabe in 1979 established that Anticollagen type II antibody as the cause for inner ear destruction in autoimmune deafness.

To identify the patients with autoimmune deafness a sensitive marker has been developed. (Western blot anti-68-kd immunoassay). The presence of this marker should warn the otolaryngologist of this condition.


Prednisolone, methotrexate and cyclophosphamide has been suggested as possible treatment modalities. Early use of 60 mg prednisolone daily for 1 month has been suggested. If methotrexate is used it should be given as oral dose of 7.5 - 20 mg weekly with folic acid. The patient should be monitored closely for signs of toxicity (complete blood count, platelet count, and BUN levels). If cyclophosphamide is used it should be administered orally in doses of 1-2mg/kg/day. These patients should take lot of fluids to prevent development of hemorrhagic cystitis for a period of 1 month.

Plasma pheresis have been used with varying results.