Rituximab (Rituxan) therapy for severe thyroid-associated ophthalmopathy diminishes IGF-1R(+) T cells.

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.

• Authors: Allison N McCoy, Denise S Kim, Erin F Gillespie, Stephen J Atkins, Terry J Smith, Raymond S Douglas
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 7 Pg. E1294-9 (Jul 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 24670080 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Rituximab
• Receptor, IGF Type 1

Topics

• Aged
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Graves Ophthalmopathy (drug therapy, immunology, metabolism)
• Humans
• Lymphocyte Count
• Male
• Middle Aged
• Receptor, IGF Type 1 (metabolism)
• Retrospective Studies
• Rituximab
• Severity of Illness Index
• T-Lymphocytes (drug effects, metabolism, pathology)
• Treatment Outcome