Autoantibody-mediated dysfunction of sympathetic neurons in guillain-barre syndrome.
OBJECTIVE
To investigate a pathologic immune response to autonomic nerve fibers in Guillain-Barré syndrome (GBS).


METHODS
We compared the effects of purified IgG from patients with GBS, multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy on transmitter synthesis and synaptic transmission in an in vitro model of sympathetic neurons and cardiomyocytes.


METHODS
Three patients with GBS, 2 with chronic inflammatory demyelinating polyradiculoneuropathy, and 2 with relapsing-remitting multiple sclerosis.


RESULTS
Incubation of sympathetic neurons with GBS-IgG resulted in an upregulation of tyrosine hydroxylase and caused a relative increase of noradrenaline levels. In cocultures of sympathetic neurons and cardiomyocytes, GBS-IgG altered the synaptic transmission, as assessed by changes in the average cardiomyocyte beat rate. These effects could be neutralized by preincubation of sympathetic neurons with intravenous immunoglobulins.


CONCLUSIONS
Our findings indicate that in GBS, circulating antibodies directed against sympathetic neurons may contribute to autonomic dysfunction via functionally relevant changes in the noradrenaline synthesis.
Lehmann
Helmar C
HC
Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf, Germany. helmar.lehmann@uni-duesseldorf.de
Jangouk
Parastoo
P
Kierysch
Eva K
EK
Meyer zu Hörste
Gerd
G
Hartung
Hans-Peter
HP
Kieseier
Bernd C
BC
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D020275:Guillain-Barre Syndrome / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000187:drug effects; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000097:blood / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects; D017783:Superior Cervical Ganglion / Q000166:cytology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000276:immunology; D014630:Vagus Nerve / Q000166:cytology
D000199:Actins; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase