Evidence for specific autoimmunity against sympathetic and parasympathetic nervous tissues in type I diabetes mellitus and the relation to cardiac autonomic dysfunction

There is growing evidence for the involvement of immunological factors in the pathogenesis of cardiac autonomic dysfunction in Type I 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 I DM patients were investigated for sympathetic and parasympathetic ganglia (CF-SG and CFPSG) 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 I 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 I DM patients). All except two Type I 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; ≤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 I DM.