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In 2002-2003, the Deafness Research Foundation supported
the research projects of two third-year medical students.
Their funding period is coming to an end but here is
a glimpse of what they have been working on…
New Direction for Thinking about Autoimmune Sensorineural
Hearing Loss by Michael Patterson, University of Pennsylvania
Autoimmune sensorineural hearing loss (AI-SHL) is a
clinical diagnosis of progressive hearing loss that
responds to steroid treatment in the absence of any
other known cause. There are no laboratory tests to
confirm this diagnosis. It is often, but not always
associated with autoimmune diseases, and the disorder
displays a variable clinical picture. Furthermore, damage
mediated by autoantibodies, the sine qua non of autoimmune
disease, has not been shown to be responsible for hearing
loss in these patients. For these reasons, it is possible
that this term encompasses several different disease
processes, some of which may be independent of the activity
of autoantibodies. A greater understanding of the pathophysiology
underlying AI-SHL promises to improve the diagnosis
and treatment of patients with this type of hearing
loss.
The MRL-Faslpr mouse, a well-studied model for the
human autoimmune disease systemic lupus erythematosus,
is also a model for AI-SHL. This mouse displays progressive
hearing loss that responds to steroid treatment. A characteristic
pattern of cellular damage, hydropic degeneration, or
cellular edema, is observed in the intermediate cells
of the stria vascularis of the inner ear. This type
of damage suggests a problem with fluid and ion homeostasis.
As in human AI-SHL, autoantibodies have not been definitively
implicated in the hearing loss observed in this mouse.
Cytokines are soluble proteins that serve to coordinate
various cellular processes, including cell differentiation,
inflammation, other functions of the immune system,
and fluid and ion homeostasis. The MRL-Faslpr mouse,
similar to some patients with systemic autoimmune disorders,
displays a gross dysregulation of cytokine production.
The researchers propose that systemic cytokine dysregulation
alters the local cytokine environment in the inner ear,
and that this local cytokine dysregulation produces
the observed cellular damage in the stria vascularis
leading to hearing loss. If true, hearing loss in this
animal, and possibly in some patients with "AI-SHL"
is not an "autoimmune" process per se, but
rather, it is "immune-mediated". This hypothesis
represents a new direction for thinking about AI-SHL
and could improve doctors' ability to diagnose and treat
patients with this problem.
The cochleae of 10 week-old “lupus” mice
and their normal controls were reacted with antibodies
for the ligand and receptors of several proinflammatory
cytokines: Il-1, TNFá, and TGFâ. The results
show that the primary site of theses proteins is the
lateral wall tissues, specifically the fibrocytes, of
the cochlea. The intensity differences between immunostaining
of the lupus and control mice are slight, possibly because
progression of lupus at 10 weeks is minimal. Finally,
receptors for some of the cytokines appear to be present
on the cells lining the blood vessels of the inner ear,
a condition that is necessary to link systemic cytokine
dysregulation with local dysregulation in the inner
ear. We are exploring this possibility in current studies.
Michael Patterson, a third-year medical student, is
working with Michael Anne Gratton, Ph.D., research assistant
professor of otolaryngology, and James C. Saunders,
Ph.D., professor of research otolaryngology, physiology,
and neuroscience, at the University of Pennsylvania,
Philadelphia.
For more information on this study, contact Michael
Patterson at the University of Pennsylvania, dpatters@mail.med.upenn.edu.
The Effects of Patterned Sound Deprivation on Auditory
Cortex Development by Edward Chang, University of California,
San Francisco
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