Allison N McCoy1, Denise S Kim, Erin F Gillespie, Stephen J Atkins, Terry J Smith, Raymond S Douglas. 1. 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.
Abstract
CONTEXT: 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. DESIGN: This was a retrospective case series assessing IGF-1R(+) T cells before and after treatment with rituximab with an 18-month follow-up. SETTING: The study was conducted at a tertiary care medical center. PATIENTS: Study participants included eight patients with severe TAO. INTERVENTIONS: Two infusions of rituximab (1 g or 500 mg each) were administered 2 weeks apart. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN: This was a retrospective case series assessing IGF-1R(+) T cells before and after treatment with rituximab with an 18-month follow-up. SETTING: The study was conducted at a tertiary care medical center. PATIENTS: Study participants included eight patients with severe TAO. INTERVENTIONS: Two infusions of rituximab (1 g or 500 mg each) were administered 2 weeks apart. MAIN OUTCOME MEASURES: 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: Aimee J Varewijck; Anita Boelen; Steven W J Lamberts; Eric Fliers; Leo J Hofland; Wilmar M Wiersinga; Joseph A M J L Janssen Journal: J Clin Endocrinol Metab Date: 2013-01-07 Impact factor: 5.958