Antibodies to L-periaxin in sera of patients with peripheral neuropathy produce experimental sensory nerve conduction deficits. J Neurochem 2002 Nov;83(3):592-600
Date
10/23/2002Pubmed ID
12390521DOI
10.1046/j.1471-4159.2002.01159.xScopus ID
2-s2.0-0036829266 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
L-Periaxin is a PDZ-domain protein localized to the plasma membrane of myelinating Schwann cells and plays a key role in the stabilization of mature myelin in peripheral nerves. Mutations in L-periaxin have recently been described in some patients with demyelinating peripheral neuropathy, suggesting that disruption of L-periaxin function may result in nerve injury. In this study, we report the presence of autoantibodies to L-periaxin in sera from two of 12 patients with diabetes mellitus (type 2)-associated neuropathy and three of 17 patients with IgG monoclonal gammopathy of undetermined significance (MGUS) neuropathy, an autoimmune peripheral nerve disorder. By comparison, anti-L-periaxin antibodies were not present in sera from nine patients with IgM MGUS neuropathy or in sera from 10 healthy control subjects. The effect of anti-L-periaxin serum antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-L-periaxin antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly (p < 0.005, n = 3) attenuated sensory-evoked compound muscle action potential (CMAP) amplitudes in the absence of temporal dispersion. In contrast, motor-evoked CMAP amplitudes and latencies were not affected by intraneural injection of sera containing anti-L-periaxin antibody. Light and electron microscopy of anti-L-periaxin serum-injected nerves showed morphologic evidence of demyelination and axon enlargement. Depleting sera of anti-L-periaxin antibodies neutralized the serum-mediated effects on nerve function and nerve morphology. Together, these data support anti-L-periaxin antibody as the pathologic agent in these serum samples. We suggest that anti-L-periaxin antibodies, when present in sera of patients with IgG MGUS- or diabetes-associated peripheral neuropathy, may elicit sensory nerve conduction deficits.
Author List
Lawlor MW, Richards MP, De Vries GH, Fisher MA, Stubbs EB JrAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAmino Acid Sequence
Animals
Autoantibodies
Blood Proteins
Cells, Cultured
Complement System Proteins
Diabetes Mellitus, Type 2
Diabetic Neuropathies
H-Reflex
Humans
Immunoglobulin G
Immunoglobulin M
Male
Membrane Proteins
Middle Aged
Molecular Sequence Data
Neural Conduction
Paraproteinemias
Peptide Fragments
Peripheral Nerves
Peripheral Nervous System Diseases
Rats
Rats, Inbred Lew
Reference Values
Sciatic Nerve
