The expression of microvesicles in the blood of patients with Graves' disease and its relationship to treatment

Clin Endocrinol (Oxf). 2016 May;84(5):729-35. doi: 10.1111/cen.12872. Epub 2015 Sep 22.

Abstract

Objective: Graves' disease (GD) is an autoimmune disease characterized by the presence of circulating autoantibodies against thyroid-stimulating hormone (TSH) receptor. Despite extensive research, the pathogenic mechanisms remain unclear. Immune responses associated with the disease may lead to cell activation/apoptosis and the release of microvesicles (MVs) into the circulation. MVs can display biological activities which may aggravate GD further. We studied immune mechanisms in GD by investigating the numbers and phenotype of circulating MVs in patients before and after antithyroid therapy with thiamazole.

Patients and measurements: Samples were obtained from 15 patients with GD in the acute phase of hyperthyroidism and following 17-26 months treatment and 14 healthy controls. MVs from platelets, endothelial cells and monocytes exposing inflammation/activation markers (P-selectin, CD40 ligand, E-selectin and HMGB1) and MVs containing nuclear molecules were measured with flow cytometry.

Results: Patients had elevated baseline values of MVs (P < 0·001 for all types of MVs), while the levels decreased during thiamazole treatment (P < 0·05 for all types of MVs). The majority of MV populations remained, however, significantly higher in patients after treatment compared to levels in controls.

Conclusions: GD patients have elevated levels of MVs that carry molecules with potential biological activities. MVs are significantly reduced after antithyroid treatment with thiamazole but still higher compared to levels in healthy controls. Assessment of MV levels and pattern may therefore provide additional information on underlying immune disturbances not obtained by measurements of hormone levels alone.

MeSH terms

  • Adult
  • Antithyroid Agents / therapeutic use
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • CD40 Ligand / metabolism
  • Cell-Derived Microparticles / drug effects
  • Cell-Derived Microparticles / metabolism
  • E-Selectin / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Extracellular Vesicles / drug effects*
  • Extracellular Vesicles / metabolism
  • Female
  • Flow Cytometry
  • Graves Disease / blood*
  • Graves Disease / drug therapy*
  • HMGB1 Protein / metabolism
  • Humans
  • Male
  • Methimazole / therapeutic use*
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism
  • P-Selectin / metabolism
  • Time Factors
  • Treatment Outcome

Substances

  • Antithyroid Agents
  • E-Selectin
  • HMGB1 Protein
  • P-Selectin
  • CD40 Ligand
  • Methimazole