title: Evidence for specific autoimmunity against sympathetic and parasympathetic nervous tissues in Type 1 diabetes mellitus and the relation to cardiac autonomic dysfunction.
abstract: There is growing evidence for the involvement of immunological factors in the pathogenesis of cardiac autonomic dysfunction in Type 1 diabetes mellitus (DM). To evaluate the presence of autoantibodies against autonomic nervous tissues and their relationship with tests of autonomic function, 64 newly diagnosed and 142 long duration Type 1 DM patients were investigated for sympathetic and parasympathetic ganglia (CF-SG and CF-PSG) autoantibodies with a complement-fixing indirect immunofluorescence technique. Five cardiac reflex tests were performed to assess autonomic function. Fifty-seven patients with neurological diseases other than diabetic neuropathy and 131 healthy control subjects were also tested for CF-SG and CF-PSG autoantibodies. CF-SG autoantibodies were observed in 47 (23%) and CF-PSG autoantibodies in 21 (10%) of 206 Type 1 DM patients (p < 0.001). In contrast, these autoantibodies were detected in 3 (5%) and 1 (2%) of patients with non-diabetic neurological diseases and 3 (2%) and 4 (3%) of control subjects (p < 0.01, p < 0.05, p < 0.0001, p < 0.05 vs Type 1 DM patients). All except two Type 1 DM patients with CF-PSG autoantibodies also presented with CF-SG autoantibodies. In diabetic patients with long duration, CF-SG autoantibodies were more frequent in patients with ECG-based cardiac autonomic neuropathy (CAN; > or =2 of 5 cardiac reflex tests abnormal) compared to patients without CAN although this did not reach statistical significance (29% vs 17%, p = 0.06). However, 4 (80%) of 5 newly diagnosed and 23 (32%) of 73 established Type 1 DM patients with abnormalities in heart rate variation during deep breathing and/or standing from lying presented with CF-SG autoantibodies compared to 12 (25%) of 58 newly diagnosed (p < 0.05) and 7 (11%) of 63 established Type 1 DM patients (p < 0.01), in whom both tests were normal. The results suggest that autoimmune factors contribute to the pathogenesis of cardiac autonomic dysfunction in Type 1 DM and that autoantibodies against sympathetic and parasympathetic nervous tissues are relatively specific for Type 1 DM.
authors.affiliation: Institute of Nutrition Science, Technical University of Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Muhr-Becker
authors.forename: A G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: A
authors.initials: A
authors.lastname: Druschky
authors.forename: G
authors.initials: G
authors.lastname: Wolfram
authors.forename: M
authors.initials: M
authors.lastname: Haslbeck
authors.forename: B
authors.initials: B
authors.lastname: Neundörfer
authors.forename: E
authors.initials: E
authors.lastname: Standl
authors.forename: O
authors.initials: O
authors.lastname: Schnell
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D015551:Autoimmunity; D001342:Autonomic Nervous System Diseases / Q000276:immunology*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003929:Diabetic Neuropathies / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005725:Ganglia, Autonomic / Q000276:immunology; D005726:Ganglia, Parasympathetic / Q000276:immunology*; D006321:Heart / Q000294:innervation; D006801:Humans; D008297:Male; D008875:Middle Aged; D013564:Sympathetic Nervous System / Q000276:immunology*