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Zimering MB, Mirkovic N, Pandya M, et al. Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes. J Endocrinol Diabetes. 2016;3(1)doi: 10.15226/2374-6890/3/1/00141.
Zimering, M. B., Mirkovic, N., Pandya, M., Zimering, J. H., Behnke, J. A., Thakker-Varia, S., Alder, J., & Donnelly, R. J. (2016). Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes. Journal of endocrinology and diabetes, 3(1), . https://doi.org/10.15226/2374-6890/3/1/00141
Zimering, Mark B, et al. "Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes." Journal of endocrinology and diabetes vol. 3,1 (2016). doi: https://doi.org/10.15226/2374-6890/3/1/00141
Zimering MB, Mirkovic N, Pandya M, Zimering JH, Behnke JA, Thakker-Varia S, Alder J, Donnelly RJ. Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes. J Endocrinol Diabetes. 2016;3(1). doi: 10.15226/2374-6890/3/1/00141. Epub 2016 Mar 08. PMID: 29796423; PMCID: PMC5963888.
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J Endocrinol Diabetes. 2016;3(1). doi: 10.15226/2374-6890/3/1/00141. Epub 2016 Mar 08.

Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes.

Journal of endocrinology and diabetes

Mark B Zimering, N Mirkovic, M Pandya, J H Zimering, J A Behnke, S Thakker-Varia, J Alder, R J Donnelly

Affiliations

  1. Medical Service (111), Veterans Affairs New Jersey Healthcare System, East Orange & Lyons, NJ, USA.
  2. Division of Endocrinology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
  3. Department of Neuroscience and Cell Biology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, USA.
  4. Molecular Resource Facility, Rutgers - New Jersey Medical School, Newark, NJ, USA.

PMID: 29796423 PMCID: PMC5963888 DOI: 10.15226/2374-6890/3/1/00141

Abstract

AIMS: To assess neuronal depolarization evoked by autoantibodies in diabetic depression compared to depolarization evoked by autoantibodies in control patients. To determine whether a subset of severe (late-onset) diabetic complications may be mediated in part by toxic immunoglobulin light chains that may increase in diabetic nephropathy.

METHODS: Protein-A eluates from plasma of 21 diabetic depression patients and 37 age-matched controls were tested for depolarization in hippocampal or immature neurons. Subsets of depolarizing or non-depolarizing autoantibodies were tested for neurite outgrowth inhibition in N2A neuroblastoma cells or the ability to modulate Ca

RESULTS: Diabetic depression (n = 21) autoantibodies caused significantly greater mean depolarization in neuroblastoma cells (

CONCLUSION: These data suggest that autoantibodies in older adult diabetic depression cause long-lasting depolarization in hippocampal neurons including adult dentate gyrus neural progenitor cells. The autoantibodies may impair adult dentate gyrus neurogenesis associated with treatment-refractory depression via several mechanisms including suppression of neurite outgrowth, and alteration of membrane excitability. Stable, toxic light chain autoantibody components may contribute to a cluster of severe (late-onset) complications characterized by dysfunction in highly vascularized tissues.

Keywords: Autoantibodies; Depression; Diabetes mellitus; Light chains; Nephropathy; Neural progenitor cells

Conflict of interest statement

Conflict of Interest The authors report no conflict of interest that would affect the objectivity of the present findings.

References

  1. J Immunol. 1995 Sep 15;155(6):3245-52 - PubMed
  2. J Neurosci. 2001 Sep 1;21(17):6782-90 - PubMed
  3. J Comp Neurol. 2000 Oct 2;425(4):479-94 - PubMed
  4. Diabetes Res Clin Pract. 2011 Jul;93(1):95-105 - PubMed
  5. Adv Cardiol. 2011;46:43-66 - PubMed
  6. J Physiol. 2002 Nov 15;545(Pt 1):81-92 - PubMed
  7. Hippocampus. 2006;16(3):239-49 - PubMed
  8. Diabetes. 1996 Sep;45(9):1209-16 - PubMed
  9. Neuron. 2005 Sep 15;47(6):803-15 - PubMed
  10. Acta Psychiatr Scand. 1995 Oct;92(4):270-3 - PubMed
  11. Blood. 2001 Aug 1;98(3):714-20 - PubMed
  12. Clin J Am Soc Nephrol. 2008 Nov;3(6):1684-90 - PubMed
  13. Diabetes Care. 2001 Jun;24(6):1069-78 - PubMed
  14. Life Sci. 2002 Nov 8;71(25):2939-59 - PubMed
  15. Schizophr Res. 1996 Mar;19(1):33-40 - PubMed
  16. Curr Biol. 2001 Jan 23;11(2):121-4 - PubMed
  17. Metabolism. 2009 Mar;58(3):393-400 - PubMed
  18. Nat Neurosci. 2002 May;5(5):438-45 - PubMed
  19. J Neurochem. 1997 Dec;69(6):2452-65 - PubMed
  20. J Immunol. 1993 Apr 15;150(8 Pt 1):3561-8 - PubMed
  21. J Biol Chem. 2008 Jul 25;283(30):20897-906 - PubMed
  22. Diabetes Care. 2014 Aug;37(8):2067-77 - PubMed
  23. Front Endocrinol (Lausanne). 2013 May 15;4:58 - PubMed
  24. Arterioscler Thromb Vasc Biol. 2001 May;21(5):785-90 - PubMed
  25. Diabetes Care. 2010 Feb;33(2):264-9 - PubMed
  26. Diabetes Care. 2012 Aug;35(8):1708-15 - PubMed
  27. Brain Res. 1997 Nov 21;776(1-2):40-50 - PubMed
  28. J Biol Chem. 2010 Nov 26;285(48):37672-82 - PubMed
  29. Mol Cell Biol. 2012 Sep;32(17):3382-91 - PubMed

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