title: Inflammation and increased myxovirus resistance protein A expression in thyroid tissue in the early stages of Hashimoto's thyroiditis.
abstract: BACKGROUND
  The role of viruses as environmental triggers for Hashimoto's thyroiditis (HT) is controversial. Thyroid epithelial cells express a variety of molecules involved in antiviral responses. This study combined histological, immunological, and virological tests to describe changes in tissue from patients with newly diagnosed and untreated HT. To study the early events, patients with positive thyroid peroxidase antibodies (TPO-Ab) and normal thyroid function were also included. This stage was defined as "prethyroiditis."
  
  
  METHODS
  Thyroid tissue was collected from 47 patients with high titers of TPO-Ab and from 24 controls. Seventeen patients had prethyroiditis, 17 had subclinical hypothyroidism, and 13 had overt hypothyroidism. The interferon (IFN)-α/β-inducible myxovirus resistance protein 1 (myxovirus resistance protein A; MxA) was used as a surrogate marker for type I IFN expression. Inflammation, expression of MxA, and the presence of the enteroviralcapsid protein (VP1) were characterized by immunohistochemistry. The presence of enterovirus (EV) RNA was examined by in situ hybridization.
  
  
  RESULTS
  The density of CD4+ T cells was increased in all three patient groups, while CD8+ T cells were increased only in patients with overt hypothyroidism. The density of plasma cells increased as the disease progressed. The density of plasmacytoid dendritic cells and the expression of MxA were significantly increased in all patient groups compared with controls (p<0.01). EV RNA was present in 11% of HT patients, but in none of the control subjects, whereas the enteroviral protein was detected in 19% and 16%, respectively.
  
  
  CONCLUSIONS
  The inflammatory reaction in the thyroid gland is a very early event in the pathogenesis of HT. The increased expression of MxA in the inflamed tissue suggests that type I IFN plays a role in disease development. Whether this is virus-dependent needs to be explored in further studies.
authors.affiliation: Hormone Laboratory, Oslo University Hospital-Aker, Oslo, Norway. sara.hammerstad@medisin.uio.no
authors.forename: Sara Salehi
authors.initials: SS
authors.lastname: Hammerstad
authors.forename: Frode Lars
authors.initials: FL
authors.lastname: Jahnsen
authors.forename: Sisko
authors.initials: S
authors.lastname: Tauriainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.forename: Trond
authors.initials: T
authors.lastname: Paulsen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Norheim
authors.forename: Knut
authors.initials: K
authors.lastname: Dahl-Jørgensen
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D002213:Capsid / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D004770:Enterovirus / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D050031:Hashimoto Disease / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D007453:Iodide Peroxidase / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000906:Antibodies; D004279:DNA, Viral; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D007453:Iodide Peroxidase; D019204:GTP-Binding Proteins