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Regulated secretion of high molecular weight hyaluronan (HA) by Graves' disease orbital cells: a modified ELISA to measure HA production

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • C.C. Krieger
  • M.C. Gershengorn


Interstitial edema caused by excess production of hyaluronan (hyaluronic acid, HA) in the retro-orbital space is a major component of Graves’ ophthalmopathy (GO). At present, there is a controversy as to whether this increased HA production is from fibroblasts/preadipocytes or adipocytes, or both. In most previous studies, HA was measured by ELISAs that used HA binding proteins (HABP) for detection. We show that the binding efficiency of HABP is a function of HA polymer size. Using a novel PAGE technique, we show that HA secreted from orbital fibroblasts/preadipocytes and adipocytes is primarily comprised of polymers > 500 kDa. We developed a modified ELISA calibrated to accurately measure HA of this size. We demonstrated that interleukin 1β-stimulated HA secretion is at least 2-fold greater than previously reported and activation of the thyroid-stimulating hormone receptor (TSHR) by an activating antibody M22 led to >3-fold increase in HA production in both fibroblasts/preadipocytes and adipocytes. These effects were not detected with the commercial ELISAs and suggest fibroblasts/preadipocytes may play a more prominent role in HA remodeling in Graves' disease than previously appreciated.

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