Type 2 diabetes with neuropathy: autoantibody stimulation of autophagy via Fas.

We reported previously that sera from patients with type 2 diabetes and neuropathy induce autophagy in human neuroblastoma (SH-SY5Y) cells. Here we report that enriched immunoglobulin fractions from a subpopulation of these patients induce autophagy and colocalization with Fas-activated death domain (FADD), a component of the Fas-activated death domain receptor signaling pathway. These effects were replicated by treatment of SY5Y cells with Fas ligand, tumor necrosis factor alpha and an agonist anti-Fas antibody. Preincubation of these sera with a soluble Fas receptor chimera (extracellular domain) markedly decreased the stimulation of autophagy. The results suggest that sera from subset of individuals with type 2 diabetes and neuropathy contain autoantibodies that activate the Fas cascade.