TY  - JOUR
A1  - Hecker, Katharina
A1  - Grüner, Julia
A1  - Hartmannsberger, Beate
A1  - Appeltshauser, Luise
A1  - Villmann, Carmen
A1  - Sommer, Claudia
A1  - Doppler, Kathrin
T1  - Different binding and pathogenic effect of neurofascin and contactin–1 autoantibodies in autoimmune nodopathies
T2  - Frontiers in Immunology
N2  - Introduction 
IgG4 autoantibodies against paranodal proteins are known to induce acute-onset and often severe sensorimotor autoimmune neuropathies. How autoantibodies reach their antigens at the paranode in spite of the myelin barrier is still unclear.

Methods 
We performed in vitro incubation experiments with patient sera on unfixed and unpermeabilized nerve fibers and in vivo intraneural and intrathecal passive transfer of patient IgG to rats, to explore the access of IgG autoantibodies directed against neurofascin-155 and contactin-1 to the paranodes and their pathogenic effect.

Results 
We found that in vitro incubation resulted in weak paranodal binding of anti-contactin-1 autoantibodies whereas anti-neurofascin-155 autoantibodies bound to the nodes more than to the paranodes. After short-term intraneural injection, no nodal or paranodal binding was detectable when using anti-neurofascin-155 antibodies. After repeated intrathecal injections, nodal more than paranodal binding could be detected in animals treated with anti-neurofascin-155, accompanied by sensorimotor neuropathy. In contrast, no paranodal binding was visible in rats intrathecally injected with anti-contactin-1 antibodies, and animals remained unaffected.

Conclusion 
These data support the notion of different pathogenic mechanisms of anti-neurofascin-155 and anti-contactin-1 autoantibodies and different accessibility of paranodal and nodal structures.
KW  - autoimmune nodopathy
KW  - IgG4
KW  - neurofascin
KW  - contactin
KW  - node of ranvier
KW  - inflammatory neuropathy
KW  - passive transfer
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/32039
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-320395
VL  - 14
ER  -