title: Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block.
abstract: Elevated levels of serum antibodies to neurofilament proteins have been associated with a variety of neurological diseases, including autoimmune disorders such as neuropathy with monoclonal gammopathy of undetermined significance (MGUS). The pathological significance of anti-neurofilament antibodies in sera of affected patients, however, remains unclear. In this study, we report our findings of polyclonal antibodies in sera from 4 of 16 IgG MGUS neuropathy patients that react strongly on immunoblot with a high molecular weight neurofilament protein (NFH). The effect of anti-NFH polyclonal antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-NFH antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly attenuated proximal-evoked motor nerve compound muscle action potential (CMAP) amplitudes in a complement-dependent manner. In contrast, ankle-evoked CMAP amplitudes were unaffected by intraneural injection of sera containing anti-NFH antibody. Anti-NFH serum-injected nerves showed changes in both axon caliber (shrinkage) and myelin ultrastructure (vesiculation and ovoid formation), suggestive of intramyelinic edema. Preincubation of sera containing anti-NFH antibody with purified NFH protein abolished immunoreactivity to NFH protein and neutralized the serum-mediated toxicity. The data suggest that anti-NFH polyclonal antibodies occurring in sera of some patients with IgG MGUS neuropathy may elicit peripheral nerve conduction block independent of the patients' IgG paraprotein. Anti-neural polyclonal antibodies in sera of IgG MGUS neuropathy patients may have a greater pathological significance than previously anticipated.
authors.affiliation: Neurology Service, Edward Hines, Jr. VA Hospital, IL 60141, USA. evan.stubbs@med.va.gov
authors.forename: Evan B
authors.initials: EB
authors.lastname: Stubbs
authors.forename: Mike W
authors.initials: MW
authors.lastname: Lawlor
authors.forename: Michael P
authors.initials: MP
authors.lastname: Richards
authors.forename: Kiran
authors.initials: K
authors.lastname: Siddiqui
authors.forename: Morris A
authors.initials: MA
authors.lastname: Fisher
authors.forename: Nirmala
authors.initials: N
authors.lastname: Bhoopalam
authors.forename: George J
authors.initials: GJ
authors.lastname: Siegel
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000368:Aged; D000818:Animals; D004576:Electromyography; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D008297:Male; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000276:immunology*; D009431:Neural Conduction / Q000187:drug effects; D016900:Neurofilament Proteins / Q000276:immunology*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000276:immunology*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: D007074:Immunoglobulin G; D016900:Neurofilament Proteins