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The Neuronal Toxic Factor in Serum of Type 1 Diabetic Patients is a Complement‐fixing Autoantibody
Author(s) -
Pittenger G. L.,
Liu D.,
Vinik A. I.
Publication year - 1995
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.1995.tb00499.x
Subject(s) - medicine , antibody , autoantibody , endocrinology , type 1 diabetes , diabetes mellitus , antigen , autoimmune disease , immunology
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 10 5 cells) compared to cells cultured with immunoglobulins from control (8.2 ± 2.3 times 10 5 cells) or Type 2 diabetic serum (7.0 ± 3.0 times 10 5 cells). The inhibitory effect (3.2 ± 0.9 times 10 5 cells) could be removed from Type 1 diabetic serum by affinity precipitation with protein A‐agarose (8.0 ± 0.8 times 10 5 cells). Mild heat denaturing of the serum reversed the inhibitory effect (3.8 ± 0.9 vs 1.4 ± 1.4 times 10 5 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.