expression + activation of NF-kappaB in nerve biopsy specimens from patients with peripheral neuropathies of different origins

[Guest guest]

Abstract from Arch Neurol. 2004 Jul;61(7):1097-1102.

Immunolocalization and Activation of Transcription Factor Nuclear Factor

{kappa}B in Dysimmune Neuropathies and Familial Amyloidotic

Polyneuropathy. (4 with CMT were in this study)

Mazzeo A, Aguennouz M, Messina C, Vita G.

Department of Neuroscience, Psychiatry, and Anesthesiology, University

of Messina, Messina, Italy.

BACKGROUND: Recently, immunoreactivity of transcription factor nuclear

factor kappaB (NF-kappaB) was found in peripheral nerves from patients

with Guillain-Barre syndrome, chronic inflammatory demyelinating

polyneuropathy (CIDP), and familial amyloidotic polyneuropathy (FAP),

suggesting a role in their pathogenesis.

OBJECTIVE: To investigate expression and activation of NF-kappaB in

nerve biopsy specimens from patients with peripheral neuropathies of

different origins.Patients Nerve biopsies from 17 patients (5 with CIDP,

3 with vasculitis, 4 with Charcot-Marie-Tooth disease, and 5 with FAP)

and 3 normal sural nerves were studied by immunocytochemistry and

Western blot of nuclear extracts for the activated form of NF-kappaB.

Nuclear factor kappaB DNA-binding activity was studied by

electrophoretic mobility shift assay.

RESULTS: Immunobinding for the activated form p65 of NF-kappaB was found

in 2% to 5% of endoneurial vessel walls, in the external myelin of 5% to

10% of fibers, and in a few axons in CIDP specimens. It was also found

in 5% to 15% of epineurial and endoneurial vessels in vasculitis

specimens and at the level of amyloid deposits in FAP nerves. Nuclear

factor kappaB immunoreactivity was not correlated to type of

inflammatory cells, but it often corresponded to the deposition of the

terminal complement complex C5b9. Western blot analysis of nuclear

extracts showed a single band corresponding to 65 kDa in all affected

nerves. Nuclear factor kappaB DNA-binding activity was revealed by

electrophoretic mobility shift assay in specimens from patients with

CIDP, vasculitis, and FAP.

CONCLUSION: Our novel findings suggest a crucial role of NF-kappaB in

inflammatory neuropathies and FAP.