PMID- 10491405
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 6
DP  - 1999 Sep
TI  - Monoclonal antibodies raised against Guillain-Barre syndrome-associated
      Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and
      paralyze muscle-nerve preparations.
PG  - 697-708
AB  - Guillain-Barre syndrome and its variant, Miller-Fisher syndrome, are acute,
      postinfectious, autoimmune neuropathies that frequently follow Campylobacter
      jejuni enteritis. The pathogenesis is believed to involve molecular mimicry
      between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 
      90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a
      ganglioside antibodies that may also react with other disialylated gangliosides
      including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C.
      jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To
      determine whether this structural mimicry results in pathogenic autoantibodies,
      we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that
      reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides.
      Immunohistology demonstrated antibody binding to ganglioside-rich sites including
      motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal 
      function, application of antibodies either ex vivo or in vivo via passive
      immunization induced massive quantal release of acetylcholine, followed by
      neurotransmission block. This effect was complement-dependent and associated with
      extensive deposits of IgM and C3c at nerve terminals. These data provide strong
      support for the molecular mimicry hypothesis as a mechanism for the induction of 
      cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious
      neuropathies.
FAU - Goodyear, C S
AU  - Goodyear CS
AD  - University Department of Neurology, Southern General Hospital, Glasgow G51 4TF,
      Scotland.
FAU - O'Hanlon, G M
AU  - O'Hanlon GM
FAU - Plomp, J J
AU  - Plomp JJ
FAU - Wagner, E R
AU  - Wagner ER
FAU - Morrison, I
AU  - Morrison I
FAU - Veitch, J
AU  - Veitch J
FAU - Cochrane, L
AU  - Cochrane L
FAU - Bullens, R W
AU  - Bullens RW
FAU - Molenaar, P C
AU  - Molenaar PC
FAU - Conner, J
AU  - Conner J
FAU - Willison, H J
AU  - Willison HJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Complement C3)
RN  - 0 (Gangliosides)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Lipopolysaccharides)
SB  - AIM
SB  - IM
EIN - J Clin Invest 1999 Dec;104(12):1771
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology
MH  - Campylobacter jejuni/*immunology
MH  - Complement C3/physiology
MH  - Cross Reactions
MH  - Female
MH  - Gangliosides/*immunology
MH  - Immunization
MH  - Immunoglobulin M/immunology
MH  - Lipopolysaccharides/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Neuromuscular Junction/*physiology
MH  - Peripheral Nerves/immunology
MH  - Polyradiculoneuropathy/*microbiology
PMC - PMC408431
EDAT- 1999/09/24 09:00
MHDA- 2000/03/04 09:00
CRDT- 1999/09/24 09:00
PHST- 1999/09/24 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 1999/09/24 09:00 [entrez]
AID - 10.1172/JCI6837 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Sep;104(6):697-708. doi: 10.1172/JCI6837.