New hope for those deaf from immune system attack

A new study may one day help those deafened by immune system attack, and possibly also lead to a test that could show which patients may be helped by immediate steroid treatment.

Normally our immune systems protect us from disease, and destroys invading microbes with a swarm of attacking cells.

But it can sometimes, for no apparent reason, also go haywire and gang up on normal tissues in our body wreaking havoc to our systems.

It seems that in thousands of people each year, the immune system attacks the inner ear, which is home to the tiny, delicate structures that allow us to hear.

Then without any prior warning, in days or weeks, patients lose their hearing in one or both ears.

Sometimes, with the help of steroids, some will get part or all of their hearing back, but many are left to cope with partial or total deafness without knowing the cause.

Why this happens is unexplainable.

However, new research at the University of Michigan's Kresge Hearing Research Institute may help more patients find out quickly if steroids will help them, or if they can be spared the drugs' harsh side effects.

The research may also extend the definition of the condition, known as autoimmune sensorineural hearing loss or AISNHL, and help more people get a firm diagnosis of what's causing their mysterious hearing loss.

The researchers studied 63 people with rapidly progressing hearing loss in Michigan, Pennsylvania and Indiana, and 20 people with normal hearing.

Although the patients were suspected of having an auto-immune cause for their hearing loss, and all received steroids, a formal diagnosis had not been given.

The researchers discovered that more than half of the hearing-loss patients had antibodies against a protein found in the inner ear, called IESCA for inner-ear supporting cell antigen.

Apparently this was a sign that their immune systems recognized it as foreign.

According to senior author Thomas Carey, Ph.D., a professor and distinguished research scientist at the U-M Medical School and department chair in the School of Dentistry, the results strongly suggest that a direct test for antibodies could accurately predict which patients will regain hearing with steroid treatment.

He does however note that such a test, is still several years away from being available to patients.

It appears that the new findings may also be important to people with systemic autoimmune disorders such as lupus or rheumatoid arthritis.

This group of people are prone to losing all or part of their hearing due to an overzealous autoimmune reaction.

Of the eight study participants who had systemic autoimmune diseases and showed signs of antibodies against IESCA, six regained their hearing after steroid treatment.

Researchers at U-M have been studying IESCA for several years in animals and have found that it may be a main target of the immune system's deafening attack on the inner ear.

IESCA is found in the supporting cells that help make up the organ of Corti, a tiny but crucial structure inside the cochlea, or inner ear.

It is here, inside the organ of Corti, that the ultra-sensitive hair cells are found.

Their movement in response to vibrations creates the nerve signals that are fed to the brain and interpreted as sounds and speech.

It has been seen that damage to the organ of Corti and hair cells, whether due to immune system attack, loud noise, trauma or medications, can diminish or destroy hearing.

By developing a monoclonal antibody, called KHRI-3, that attaches to IESCA in the inner ear, and can be detected in living animal systems and cell cultures, it has allowed the researchers to study IESCA's role in hearing loss in animal models, and show that damage to the inner ear caused by antibodies to IESCA can destroy hearing.

The KHRI-3 antibody creates a staining pattern that resembles a line of tiny wine glasses when it binds to IESCA in the organs of Corti of guinea pigs.

The U-M has patent applications pending in the U.S. and overseas, but Carey says the development of a clinical test for patient antibody to IESCA will take time.

In the new study, the researchers tested blood from the 63 patients and 20 normal controls with two tests: a Western blot test and an immunofluorescence (IF) test based on KHRI-3.

They then correlated the results of those two tests with patients' response to steroid treatment, based on standard criteria and the results of hearing tests performed before and after treatment.

They also considered patients' other autoimmune diseases, the length and pace of hearing loss progression before treatment, and age and gender.

Thirty of the patients were female, and 33 male; their average age was 47, which reflects the young age at which AISNHL typically begins.

Twenty-six had lost hearing in both ears, the rest in the left or right ear.

They had no known cause for hearing loss, and most had lost their hearing gradually over weeks, though eight had lost it over hours or days.

Many also had dizziness, ringing or a sensation of fullness in their ears.

In all, half regained some or all of their hearing after steroid treatment.

The two different blood tests weren't always consistent, results were the same in 47 patients, both positive or both negative, but different in 16.

But the IF test appeared to give a more specific response to steroid treatment: patients who had a positive IF test result were three times more likely to improve after steroid treatment than those with negative IF results.

Combining the two tests proved even more predictive: 54 percent of those who had positive results on both tests improved after steroid, compared with 10 percent of those who had two negative results.

As a point of interest, Carey notes that almost all of the patients who had sudden hearing loss over hours or days had antibodies, and nearly all improved with steroids.

Carey suggests that since this kind of rapid-onset hearing loss has historically been excluded from the formal definition of AISNHL, the definition may need to be re-examined in light of the strong evidence for an immune-system cause in these patients.

The research was funded by the Autoimmune Sensorineural Hearing Loss Research Fund, the Ruth and Lynn Townsend Fund, a gift from the Holden Foundation, the Deafness Research Foundation and the National Institutes of Health.

It is published in the August issue of the Archives of Otolaryngology - Head and Neck Surgery.