The long-term objective of this proposal is to better understand how immunologic mechanisms may damage the nervous system and cause neuromuscular paralysis.
The specific aim i s to determine the mechanism by which infection with Campylobacter jejuni triggers an immunologic response that results in production of antibodies against one or more myelin proteins present in peripheral nerve. Guillain-Barre Syndrome (GBS) is the most common cause of acute neuromuscular paralysis in both adults and children in the U.S.; however, the etiology remains unknown. Increased understanding of the pathogenesis of GBS ultimately may lead to effective prevention strategies as well as control of the severity of illness. The hallmark of GBS is segmental demyelination of peripheral nerves with mononuclear infiltrates and edema. Recent studies suggest GBS frequently is preceded by infection with C. jejuni infection. Humoral immune responses to C. jejuni infection and cross-reactivity with host structures may be operative in the pathogenesis of C. jejuni- associated GBS and AMAN. This proposal will attempt to answer the following questions: 1. Does C. jejuni infection play a role in the Guillain-Barre-like syndrome, acute motor axonal neuropathy (AMAN)? 2. In the U.S., is Penner serotype 019 the predominant C. Jejuni serotype associated with GBS?. 3. If so, why is Penner serotype 019 associated with GBS and what are the key bacterial antigens? 4. Does infection with C. jejuni trigger an immunologic response resulting in auto-antibodies directed toward one or more myelin proteins?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001709-02
Application #
2259798
Study Section
NST-2 Subcommittee (NST)
Project Start
1993-12-01
Project End
1998-01-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212