Rituximab (Rituxan) Therapy for Severe Thyroid-Associated Ophthalmopathy Diminishes IGF-1R+ T Cells

Abstract

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. 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. This was a retrospective case series assessing IGF-1R(+) T cells before and after treatment with rituximab with an 18-month follow-up. The study was conducted at a tertiary care medical center. Study participants included eight patients with severe TAO. Two infusions of rituximab (1 g or 500 mg each) were administered 2 weeks apart. Quantification of IGF-1R(+) T cells using flow cytometry was measured. 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. 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.