Autoantibodies to Autonomic Nerves Associated With Cardiac and Peripheral Autonomic Neuropathy

OBJECTIVE: This study examines whether autonomic nerve autoantibodies (ANabs) are associated with development of autonomic neuropathy using a prospective study design. RESEARCH DESIGN AND METHODS: A group of type 1 diabetic patients were followed prospectively with regard to autonomic nerve function on four occasions. At the third examination, 41 patients were tested for ANabs (complement-fixing autoantibodies to the sympathetic ganglion, vagus nerve, and adrenal medulla), and the results were related to cardiac autonomic nerve function (heart rate variation during deep breathing [expiration/inspiration ratio] and heart-rate reaction to tilt [acceleration and brake index]) and to peripheral sympathetic nerve function (vasoconstriction after indirect cooling [vasoconstriction index]). RESULTS: ANabs were detected in 23 of 41 (56%) patients at the third examination. Compared with patients without ANabs (ANabs-), patients with ANabs (ANabs+) showed significantly higher frequencies of at least one abnormal cardiac autonomic nerve function test at the third examination (17 of 23 [74%] vs. 7 of 18 [39%]; P = 0.03) and fourth examination (15 of 21 [71%] vs. 4 of 16 [25%]; P < 0.01). In contrast, there was no similar difference at the first or second examination. The relative risk for ANabs(+) patients to develop cardiac autonomic neuropathy at follow-up was 7.5 (95% CI 1.72-32.80). The vasoconstriction index was more abnormal in ANabs+ than in ANabs- patients at the fourth examination (median 1.40 [interquartile range 1.58] vs. 0.35 [2.05]; P = 0.01). CONCLUSIONS: ANabs were associated with future development of cardiac and peripheral autonomic neuropathy in diabetic patients, implying an etiological relationship between nervous tissue autoimmunity and these diabetes complications.