title: The expression of microvesicles in the blood of patients with Graves' disease and its relationship to treatment.
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.
  
  
  METHODS
  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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Mobarrez
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mirna
authors.initials: M
authors.lastname: Abraham-Nordling
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.|Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Katherina
authors.initials: K
authors.lastname: Aguilera-Gatica
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Friberg
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.|Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Antovic
authors.affiliation: Medical Research Service, Durham VA Hospital, Durham, NC, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Pisetsky
authors.affiliation: Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gun
authors.initials: G
authors.lastname: Jörneskog
authors.affiliation: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallen
mesh_terms: D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy*; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D013956:Antithyroid Agents; D019040:E-Selectin; D024243:HMGB1 Protein; D019007:P-Selectin; D023201:CD40 Ligand; D008713:Methimazole