title: Rituximab (Rituxan) therapy for severe thyroid-associated ophthalmopathy diminishes IGF-1R(+) T cells.
abstract: BACKGROUND
  Rituximab depletes CD20(+) B cells and has shown potential benefit in thyroid-associated ophthalmopathy (TAO). The impact of rituximab on T cell phenotype in TAO is unexplored.
  
  
  OBJECTIVE
  The objective of the study was to quantify the abundance of IGF-I receptor-positive (IGF-1R(+)) CD4 and CD8 T cells in active TAO before and after treatment with rituximab.
  
  
  METHODS
  This was a retrospective case series assessing IGF-1R(+) T cells before and after treatment with rituximab with an 18-month follow-up.
  
  
  METHODS
  The study was conducted at a tertiary care medical center.
  
  
  METHODS
  Study participants included eight patients with severe TAO.
  
  
  METHODS
  Two infusions of rituximab (1 g or 500 mg each) were administered 2 weeks apart.
  
  
  METHODS
  Quantification of IGF-1R(+) T cells using flow cytometry was measured.
  
  
  RESULTS
  Eight patients with moderate to severe TAO [mean pretreatment clinical activity score (CAS) 5.1 ± 0.2 (SEM)] were treated. Four to 6 weeks after treatment, CAS improved to 1.5 ± 0.3, whereas the proportion of IGF-1R(+) CD3(+) T cells declined from 41.9% to 28.3% (P = .004). The proportion of IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) T cells declined 4-6 weeks after treatment (from 45.6% to 21.5% and from 32.0% to 15.8%, P = .003 and P = .001, respectively). In two patients, IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) subsets approximated pretreatment levels after 16 weeks.
  
  
  CONCLUSIONS
  Frequency of IGF-1R(+) T cells in patients with TAO declines within 4-6 weeks after rituximab treatment. This phenotypic shift coincides with clinical improvement. Thus, assessment of the abundance of IGF-1R(+) T cells in response to rituximab may provide a biomarker of clinical response. Our current findings further implicate the IGF-1R pathway in the pathogenesis of TAO.
authors.affiliation: Department of Ophthalmology and Visual Sciences (A.N.M., D.S.K., E.F.G., S.J.A., T.J.S., R.S.D.), Kellogg Eye Center, University of Michigan, Department of Internal Medicine (T.J.S.), University of Michigan Medical School, and Veterans Affairs Medical Center (R.S.D.), Ann Arbor, Michigan 48105.
authors.forename: Allison N
authors.initials: AN
authors.lastname: McCoy
authors.forename: Denise S
authors.initials: DS
authors.lastname: Kim
authors.forename: Erin F
authors.initials: EF
authors.lastname: Gillespie
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Atkins
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Douglas
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies; D000069283:Rituximab; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D017526:Receptor, IGF Type 1