title: Relationship between longitudinal behaviour of some markers of eye autoimmunity and changes in ocular findings in patients with Graves' ophthalmopathy receiving corticosteroid therapy.
abstract: OBJECTIVE
  To investigate whether variations over time of TSH-receptor antibodies (TRAb) and antibodies against G2s (G2sAb) and extraocular muscles (EMAb) can predict worsening of ophthalmopathy in Graves' patients treated with intravenous glucocorticoid (IVGC) therapy.
  
  
  METHODS
  Of 65 consecutive patients with treated Graves' disease and severe and active ophthalmopathy (GO) chosen to undergo IVGC treatment, only 57 patients, persistently euthyroid under methimazole therapy, were studied longitudinally for ocular parameters, TRAb, G2sAb and EMAb before therapy, at the end of therapy and, subsequently, every month for 21 months.
  
  
  METHODS
  TRAb was detected by radioimmunoassay (RIA), G2sAb by enzyme-linked immunosorbent assay (ELISA) and EMAb by indirect immunofluorescence.
  
  
  RESULTS
  Forty-three out of 57 patients (75.4%, group 1) responded positively to therapy [improvement in diplopia and decrease in proptosis and clinical activity score (CAS)] but 14 (24.6%) did not (group 2). During follow-up after IVGC therapy, 12 out of 43 patients in group 1 (28%) showed a worsening in GO (group 1a), while 31 (72%) had stable ocular conditions or further improvement (group 1b). At the start of the study, TRAb, G2sAb and EMAb were not significantly different among the three groups. At the end of IVGC therapy TRAb levels decreased significantly with respect to starting values in all three groups of patients, whereas G2sAb and EMAb decreased significantly in groups 1a and 1b but not in group 2. During the subsequent follow-up, 10 patients in group 1a one/two months before and all 12 patients at the time of GO worsening showed an increase in G2sAb and EMAb but not in TRAb, which were consistently absent or present at low titre in all patients in this group. In group 1b TRAb, G2sAb and EMAb further decreased or became negative during the follow-up period. In all patients, TRAb were positively correlated with both CAS and proptosis only at the start of the study; by contrast, a significant correlation between both G2sAb and EMAb and diplopia was observed in groups 1a and 1b at all the times during the study, except one/two months before the worsening of GO in group 1a.
  
  
  CONCLUSIONS
  Our results indicate that TRAb, G2sAb and EMAb can be considered sensitive markers of Graves' ophthalmopathy during the initial stages of ophthalmopathy, but that only G2sAb and EMAb seem to be good predictive markers of the outcome in patients after corticosteroid therapy. Thus, taking into account the cost/benefit ratio, a longitudinal evaluation of either EMAb or G2sAb could be useful in monitoring the intravenous glucocorticoid therapy in patients with severe and active ophthalmopathy to predict a possible worsening of Graves' ophthalmopathy.
authors.affiliation: Chair of Endocrinology, Department of Clinical and Experimental Medicine and Surgery 'F. Magrassi, A. Lanzara', Second University of Naples, Italy. annamaria.debellis@unina2.it
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Bellis
authors.forename: Antonio
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Marisa
authors.initials: M
authors.lastname: Conte
authors.forename: Concetta
authors.initials: C
authors.lastname: Coronella
authors.forename: Stefano
authors.initials: S
authors.lastname: Solimeno
authors.forename: Silvia
authors.initials: S
authors.lastname: Perrino
authors.forename: Daniela
authors.initials: D
authors.lastname: Sansone
authors.forename: Mariangela
authors.initials: M
authors.lastname: Guaglione
authors.forename: Jack R
authors.initials: JR
authors.lastname: Wall
authors.forename: Antonio
authors.initials: A
authors.lastname: Bellastella
mesh_terms: D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004172:Diplopia / Q000188:drug therapy; D005094:Exophthalmos / Q000188:drug therapy; D005123:Eye / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008713:Methimazole / Q000627:therapeutic use; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000276:immunology; D018709:Statistics, Nonparametric
chemical_list: D013956:Antithyroid Agents; D001323:Autoantibodies; D015415:Biomarkers; D005136:Eye Proteins; C406963:G2s protein, human; D005938:Glucocorticoids; D008565:Membrane Proteins; D011989:Receptors, Thyrotropin; D008713:Methimazole; D008775:Methylprednisolone