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.
Towns
Roberto
R
Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.
Guo
Chunfang
C
Shangguan
Yu
Y
Hong
Shuangsong
S
Wiley
John W
JW
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D001343:Autophagy / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009447:Neuroblastoma / Q000473:pathology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019014:fas Receptor