Peripherin-IgG association with neurologic and endocrine autoimmunity.
Peripherin-IgG has been reported a pertinent autoantibody in non-obese type 1 diabetic (NOD) mice. However, it has not previously been recognized in any human disease. In blinded evaluation of serum for markers of neurological autoimmunity in a high-volume diagnostic laboratory, we incidentally identified 26 patients (61% female) with an IgG that bound selectively to neural elements in enteric ganglia, sympathetic nerve trunks and discrete nerve tracts in mid-brain and hind-brain. The target antigen was identified as peripherin, a 55kDa - type III intermediate filament protein. Review of clinical histories revealed that 54% of seropositive patients had dysautonomia (predominantly gastrointestinal dysmotility), 30% had neuropathies with varied sensory symptoms and 35% had clinical or serological evidence of endocrinopathy (type 1 diabetes, thyroiditis or premature ovarian failure). Collectively, 73% had autonomic dysfunction or endocrinopathy. None of 173 healthy subjects was seropositive. Subsequent western blot evaluation of archival sera from patients with small fiber/autonomic neuropathies (with or without endocrinopathy) revealed a 33% seropositivity rate for peripherin-IgG. Our further demonstration that peripherin-immunoreactive autonomic fibers in pancreas, thyroid and ovary are juxtaposed to endocrine epithelium, complement our clinical observations in suggesting that neuronal elements may be a pertinent initial target for immune attack in multiple forms of endocrine autoimmunity (intermolecular epitope spreading). It remains to be determined whether or not peripherin-IgG is predictive for development of small fiber neuropathy (autonomic or somatic).
Chamberlain
Jayne L
JL
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Pittock
Sean J
SJ
Oprescu
Anna-Maria
AM
Dege
Carissa
C
Apiwattanakul
Metha
M
Kryzer
Thomas J
TJ
Lennon
Vanda A
VA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies; D001324:Autoantigens; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D004703:Endocrine System / Q000276:immunology*; D005260:Female; D020275:Guillain-Barre Syndrome; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007381:Intermediate Filament Proteins / Q000097:blood / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology*; D064531:Peripherins; D054969:Primary Dysautonomias; D051381:Rats
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007074:Immunoglobulin G; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins