Bystander damage: In this theory damage to the inner ear causes cytokines to be released which provoke, after a delay, additional immune reactions. This theory might explain the attack/remission cycle of disorders such as Meniere's disease. There is evidence for cytokines in the cochlea including interleukin-1A, TNF-alpha, (Adams, 2002). Drugs that block TNF such as etanercept seem to be potentially effective in AIED (Rahmen et al, 2001). The endolymphatic sac lumen expresses TNF-alpha (Satoh et al, 2003), which may be another way wherebye Meniere's disease is linked to AIED. Other autoimmune disorders such as Crohn's disease also seem to be linked to TNF, and other ear diseases such asotosclerosis also are linked to TNF-alpha.(Karosi, Konya et al. 2005)
Cross-reactions: In this theory, antibodies or rogue T-cells cause accidental inner ear damage because the ear shares common antigens with a potentially harmful substance, virus or bacteria that the body is fighting off. This is presently the favored theory of AIED. COCH5B2 has recently been reported to be a target antigen in AIED (Boulassel et al, 2001).
Intolerance: The ear, like the eye may be only an partially "immune privileged" locus, meaning that the body may not know about all of the inner ear antigens, and when they are released (perhaps following surgery or an infection), the body may wrongly mount an attack on the "foreign" antigen.
In the eye, there is a syndrome called "sympathetic ophthalmia", where following a penetrating injury to one eye, the other eye may go blind. The corresponding situation in the ear would be to go deaf in one ear, following trauma or surgery performed on the opposite ear. This theory is not presently in favor for the ear. Nevertheless, over about 20 years of practice the author of this page has seen several patients who develop ear disease in a delayed fashion in the opposite ear treated for anacoustic neuroma, including one patient following gamma knife "surgery". There have also been cases reported of development of AIED in the opposite ear after surgery forMeniere's disease (Ochoa and Weider, 2003), 11 years after a temporal bone fracture (ten Cate and Bachor, 2005), and in 2 of 148 patients after stapes surgery (Richards et al, 2002). Lacking much organized data other than the stapes study, and considering our personal observations, we suspect that this occurs in about 1% of patients in which inner ear antigen is released into the body.
Genetic factors: There is evidence that genetically controlled aspects of the immune system may increase or otherwise be associated with increased susceptibility to common hearing disorders such as Menieres disease. Bernstein and associates reported that 44% of patients with Menieres,otosclerosis and striatal presbyacusis had one particular extended MHC haplotype (Dqw2-Dr3-c4Bsf-C4A0-G11: 15-Bf:0.4-C2a-HSP70:7.5-TNF), compared to only 7% of controls. Sudden hearing loss in Koreans that does not recover is also associated with HLA-DRB1*04, DQA1 03 and 05 (Yeo et al, 1999; Yeo et al, 2001). The author has also found an association (in the US) with certain types of HLA-types and variants of vertigo in caucasians (unpublished). On the other hand, a recent study by Lopez-Escamez and others performed in Spain found no difference in HLA antigens between 54 patients with definate MD and 534 normal controls (Lopez Escamez et al, 2002). The genetic background of HLA studies is important and it is possible that one group might find HLA differences which are not found in another.
These data are thus conflicted. If there is indeed an association with HLA, at least in certain populations, it would suggest that more of Menieres disease and other progressive syndromes may be caused by immune dysfunction than is presently generally thought. It is important to remember that HLA-typing is relevant when considered in the context of the patient's genetic background. In other words, studies of Korean subjects for example, such as reported by Yeo, may not apply to persons of non-Korean ethnicity.