Loss of Schwann cell plasticity in chronic inflammatory demyelinating polyneuropathy (CIDP).
BACKGROUND
Chronic inflammatory demyelinating polyneuropathy (CIDP) is often associated with chronic disability, which can be accounted to incomplete regeneration of injured axons. We hypothesized that Schwann cell support for regenerating axons may be altered in CIDP, which may account for the poor clinical recovery seen in many patients.


METHODS
We exposed human and rodent Schwann cells to sera from CIDP patients and controls. In a model of chronic nerve denervation, we transplanted these conditioned Schwann cells intraneurally and assessed their capacity to support axonal regeneration by electrophysiology and morphometry.


RESULTS
CIDP-conditioned Schwann cells were less growth supportive for regenerating axons as compared to Schwann cells exposed to control sera. The loss of Schwann cell support was associated with lower levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in CIDP sera and correlated with altered expression of c-Jun and p57kip2 in Schwann cells. The inactivation of these regulatory factors resulted in an altered expression of neurotrophins including BDNF, GDNF, and NGF in CIDP-conditioned Schwann cells in vitro.


CONCLUSIONS
Our study provides evidence that pro-regenerative functions of Schwann cells are affected in CIDP. It thereby offers a possible explanation for the clinical observation that in many CIDP patients recovery is incomplete despite sufficient immunosuppressive treatment.
Department of Neurology, University Hospital of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne, Cologne, Germany.
Abhijeet R
AR
Joshi
Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
Laura
L
Holtmann
Department of Neurology, University Hospital of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne, Cologne, Germany.
Ilja
I
Bobylev
Department of Neurology, University Hospital of Cologne, Cologne, Germany.
Christian
C
Schneider
Department of Neurology, University Hospital of Cologne, Cologne, Germany.
Christian
C
Ritter
Institute of Neuropathology, RWTH Aachen University, Aachen, Germany.
Joachim
J
Weis
Department of Neurology, University Hospital of Cologne, Cologne, Germany. helmar.lehmann@uk-koeln.de.|Center for Molecular Medicine Cologne, Cologne, Germany. helmar.lehmann@uk-koeln.de.
Helmar C
HC
Lehmann
CIDP; Chronic denervation; GM-CSF; Schwann cell plasticity
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