title: Anti-endothelial and anti-neuronal effects from auto-antibodies in subsets of adult diabetes having a cluster of microvascular complications.
abstract: OBJECTIVE
  To test autoantibodies from subsets of diabetes with painful neuropathy, maculopathy and nephropathy for effects in neurons.
  
  
  METHODS
  Protein-A eluates from plasma of 27 diabetic and 19 age-matched controls were tested for effects on endothelial cell survival, and neurite outgrowth in rat pheochromocytoma PC12 cells. Painful diabetic neuropathy or control autoantibodies were compared for binding to PC12-derived heparan sulfate proteoglycans. The mechanism of the effects from pathologic autoantibodies was investigated by changes in intracellular calcium in endothelial cells, whole cell current in neurons, or using the Rho kinase inhibitor Y27632.
  
  
  RESULTS
  Autoantibodies from diabetic patients with maculopathy, nephropathy, and painful neuropathy (n=5) caused significantly greater mean inhibition of neurite outgrowth (p<0.005) than diabetic or control patients with fewer or no complications (n=30). Painful diabetic autoantibodies (3 μg/mL) bound neuronal heparan sulfate proteoglycan (HSPG) more than autoantibodies from diabetic or control subjects without painful neuropathy (p<.0001). Inhibition of PC12 neurite outgrowth by the painful neuropathy antibodies was completely prevented by 1 μM concentrations of Y27632.
  
  
  CONCLUSIONS
  These results suggest anti-endothelial and anti-neuronal effects from auto-antibodies in a subset of diabetic patients with a cluster of microvascular complications.
authors.affiliation: Medical Service, Department of Veterans Affairs New Jersey Health Care System, Lyons, NJ, United States. mark.zimering@med.va.gov
authors.forename: Mark B
authors.initials: MB
authors.lastname: Zimering
authors.forename: Janet
authors.initials: J
authors.lastname: Alder
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Donnelly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000378:metabolism; D000577:Amides / Q000627:therapeutic use; D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology* / Q000627:therapeutic use*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004594:Electrophysiology; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D011471:Prostatic Neoplasms / Q000276:immunology; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000418:Albumins; D000577:Amides; D001323:Autoantibodies; D019812:Heparan Sulfate Proteoglycans; D011725:Pyridines; D016222:Fibroblast Growth Factor 2; C108830:Y 27632