MI014-07 Development of Murine models for Study of Guillain Barre Syndrome

Campylobacter jejuni  Serious disease sequelae can be triggered by infection including acute  neuropathies, Guillain Barré Syndrome (GBS) and Miller Fisher Syndrome (MFS). In the US, mean C.  annual incidence rate of GBS is 1.3 cases/100,000 population; the risk of GBS is ~1 case/1000 jejuni  infections. 5% of GBS patients die and in survivors, life-long disability may result. Previous work C.  in patients and animal models (chicken, rat) has shown that molecular mimicry occurs between jejuni  lipo-oligosaccharides (LOS) and peripheral nerve gangliosides leading to anti-ganglioside antibodies. However, murine models are needed to study GBS pathogenesis and the roles played by C. jejuni host and pathogen genetics. We will develop a murine model(s) of autoimmune sequelae of infection that can be used 1) to dissect the mechanisms of initiation of autoimmunity and 2) to serve as a treatment and prevention surrogate for GBS patients. Our first aim is to identify autoimmune C. jejuni sequelae of infection in mice (C57BL/6, NOD or C3H genotypes). We will A) determine C. jejuni whether mice produce autoantibodies to gangliosides or T cells reactive to myelin following C.infection with strains having different outer membrane ganglioside mimics, B) determine whether jejuni  infected mice exhibit neurological signs and peripheral nerve lesions consistent with GBS, and C) determine whether autoantibody or autoreactive T cells transfer the response to naïve mice. Our second aim is to identify associations between autoimmune sequelae and variability in the LOS of the C. jejuni C. challenge strains, A) to determine whether autoimmune sequelae vary with differences in jejuni C. jejuni C. LOS profiles, and B) to associate differences in LOS profiles with differences in the jejuni  LOS chromosomal region.