title: Graves' orbitopathy, idiopathic orbital inflammatory pseudotumor and Epstein-Barr virus infection: a serological and molecular study.
abstract: OBJECTIVE
  One of the hypotheses on the pathogenesis of autoimmune diseases, including Graves' disease (GD) and Graves' orbitopathy (GO), involves bacterial or viral infections. Recently, Epstein-Barr virus (EBV) has been proposed to play a role in the pathogenesis of idiopathic orbital inflammatory pseudotumor (IOIP) in Asians. The aim of the present study was to investigate the possible association of GO with EBV infection/exposure, as compared with IOIP, using serum and tissue samples, as well as primary cultures of orbital fibroblasts.
  
  
  METHODS
  Thirty-one patients were studied, including four with IOIP, ten with GO, nine with GD without GO and eight control patients without IOIP, GD and GO. All patients with IOIP and GO underwent orbital decompression. Control patients underwent palpebral surgery. Fibroadipose orbital tissue samples were collected. Serum anti-EBV antibodies were measured in all patients. EBV-DNA was measured in blood samples, orbital tissue samples and primary cultures of orbital fibroblasts.
  
  
  RESULTS
  Serum assays showed that the vast majority of patients have had a previous exposure to EBV, but no one had an acute infection. EBV-DNA was detected in ~40% of blood samples from GO, GD and control patients, but in none of the IOIP samples. EBV-DNA was not detected in any of the orbital tissue samples tested or in primary cultures of orbital fibroblasts.
  
  
  CONCLUSIONS
  EBV infection does not seem to be associated with GD, GO and IOIP in Caucasians. Whether EBV is involved in IOIP in Asians or other populations remains to be confirmed.
authors.affiliation: Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Leo
authors.affiliation: Division of Virology, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Maggi
authors.affiliation: Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: G R
authors.initials: GR
authors.lastname: Dottore
authors.affiliation: Department of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Casini
authors.affiliation: Division of Virology, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mazzetti
authors.affiliation: Division of Virology, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pistello
authors.affiliation: Department of Surgical, Medical and Molecular Pathology, ENT Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sellari-Franceschini
authors.affiliation: Department of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nardi
authors.affiliation: Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Vitti
authors.affiliation: Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
authors.affiliation: Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy. michele.marino@med.unipi.it.
authors.forename: M
authors.initials: M
authors.lastname: Marinò
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications / Q000821:virology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D005500:Follow-Up Studies; D049970:Graves Ophthalmopathy / Q000097:blood / Q000150:complications / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016727:Orbital Pseudotumor / Q000097:blood / Q000150:complications / Q000821:virology*; D011379:Prognosis
chemical_list: D004279:DNA, Viral
keywords: Epstein–Barr virus; Graves’ disease; Graves’ orbitopathy; Idiopathic inflammatory pseudotumor; Thyroid