EVIDENCE FOR SPECIFIC AUTOIMMUNITY AGAINST SYMPATHETIC AND PARASYMPATHETIC NERVOUS TISSUES IN TYPE-1 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 1 diabet es mellitus (DM). To evaluate the presence of autoantibodies against a utonomic nervous tissues and their relationship with tests of autonomi c function, 64 newly diagnosed and 142 long duration Type 1 DM patient s were investigated for sympathetic and parasympathetic ganglia (CF-SG and CF-PSG) autoantibodies with a complement-fixing indirect immunofl uorescence technique. Five cardiac reflex tests were performed to asse ss 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 wer e detected in 3 (5%) and 1 (2%) of patients with non-diabetic neurolog ical 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 Typ e 1 DM patients with CF-PSG autoantibodies also presented with CF-SG a utoantibodies. In diabetic patients with long duration, CF-SG autoanti bodies were more frequent in patients with ECG-based cardiac autonomic neuropathy (CAN; greater than or equal to 2 of 5 cardiac reflex tests abnormal) compared to patients without CAN although this did not reac h 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 w ith abnormalities in heart rate variation during deep breathing and/or standing from lying presented with CF-SG autoantibodies compared to 1 2 (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 re sults suggest that autoimmune factors contribute to the pathogenesis o f cardiac autonomic dysfunction in Type 1 DM and that autoantibodies a gainst sympathetic and parasympathetic nervous tissues are relatively specific for Type 1 DM. (C) 1998 John Wiley & Sons, Ltd.