Complement-Fixing Antibodies to Sympathetic and Parasympathetic Tissuesin IDDM: Autonomic Brake Index and Heart-Rate Variation

We describe herein complement-fixing anti-adrenal medullary (CF-ADM) andanti-sympathetic ganglia (CFSG) antibodies in insulin-dependent diabetes mellitus (IDDM). This study describes complement-fixing antivagus (CF-V) nerve antibodies and their relationship to the cardiovascular autonomic brake index (a measure of transient decrease in heart rate during the 1st min after a tilt), and R-R interval variation with deep breathing. CF-V was detectable in 7 of 83 (8.4%) subjects with IDDM aged 1.5–65.5 yr (mean ± SE 28.7± 1.8 yr) and duration of diabetes 0–47 yr (11.8 ± 1.4 yr). Seventy-six nondiabetic subjects (aged 10–65 yr) all had negative CF-V scores. CF-V scores correlated with CF-ADM (0–16 yr of IDDM, r = 0.61, P < 0.0001) and CF-SG (r = 0.39, P < 0.05). Seventy IDDM subjects (aged 28 ± 5 yr, duration of diabetes 17 ± 3 yr) without proteinuria or proliferative retinopathy were screened for CF-ADM, CF-SG, and CF-V antibodies. Five of 70 (7.1%) had CF-SG only (negative for CF-ADM and CF-V). Brake indices ranged from 14.7 to 51.3 (37.3 ± 6.9). Three of 70 (4.2%) had CF-ADM only, with brake indices from 26.9 to 45.1 (32.9 ± 6.1). Four of 70 (5.7%) had CF-V antibodies only, with brake indices of 12.7–17.3 (15.1 ± 1.1). Subjects with CF-SG or CF-ADM (antisympathetic) had higher brake indices than subjects with CF-V (anti-parasympathetic) antibodies (P < 0.03). Subjects with CF-SG had higher brake indices than those with CF-V (P < 0.04). The heart-rate variation with deep breathing was 23.3 ± 10.0 in subjects with CF-V and 45.66 ± 5.1 in the CF-SG⁺ and/or CF-ADM⁺ group (P < 0.03). This study demonstrates CF-V antibodies in IDDM and their association with a lower brake index and R-R interval variation compared with patients with sympathetic nervous system autoimmunity.