The Neuronal Toxic Factor in Serum of Type 1 Diabetic Patients is a Complement‐fixing Autoantibody

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Abstract
Type 1 diabetes is an autoimmune disease resulting in destruction of pancreatic β cells. Many of the pancreatic β cell autoantigens are also neuronal cell components. Using adrenergic neuroblastoma cells, we have previously demonstrated that humoral mechanisms may contribute to the development of diabetic neuropathy in Type 1 patients. We hypothesize that the toxic factor in Type 1 diabetic serum is an immunoglobulin. When neuroblastoma cells were exposed to immunoglobulins precipitated from serum of Type 1 diabetes patients with neuropathy, cell growth was significantly inhibited by day 5 (3.8 ± 2.4 times 105 cells) compared to cells cultured with immunoglobulins from control (8.2 ± 2.3 times 105 cells) or Type 2 diabetic serum (7.0 ± 3.0 times 105 cells). The inhibitory effect (3.2 ± 0.9 times 105 cells) could be removed from Type 1 diabetic serum by affinity precipitation with protein A‐agarose (8.0 ± 0.8 times 105 cells). Mild heat denaturing of the serum reversed the inhibitory effect (3.8 ± 0.9 vs 1.4 ± 1.4 times 105 cells), indicating a requirement for complement. Immunofluorescent labelling with anti‐IgG secondary antibody of cells exposed to Type 1 diabetic serum indicated recognition of a membrane‐bound antigen. The studies in this report support the hypothesis that autoimmune neuronal destruction may contribute to the development of diabetic autonomic neuropathy in patients with Type 1 diabetes.