Publications (2)4.95 Total impact
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Article: Biologic therapeutics in thyroid-associated ophthalmopathy: translating disease mechanism into therapy.
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ABSTRACT: Graves' disease (GD) is a systemic autoimmune disease which targets the thyroid, orbit, and skin. Thyroid-associated ophthalmopathy (TAO) refers specifically to the orbital and periorbital manifestations of GD. Several important concepts have emerged from our enhanced understanding of the molecular mechanisms of the disease. Considerable debate remains concerning the specific identity and roles of inflammatory T-cell subsets, soluble and contact-mediated signalling, and autoantigens driving TAO. However B and T lymphocytes appear central in the process through production of disease mediators including activating autoantibodies to the thyrotropin receptor and insulin-like growth factor-1 receptor; cytokines including IL-1beta, IL-6, and IL-16; and chemokines including RANTES. Many of these molecules appear central to the inflammation, accumulation of extracellular matrix macromolecules, and fibrosis in the disease. Novel therapeutics targeting other autoimmune diseases may provide an opportunity for disrupting disease pathogenesis. It is imperative that agents targeting B-and T-cell functions be further evaluated in the treatment of aggressive forms of TAO utilizing multicenter clinical trials that allow adequate statistical power and sample size.Thyroid: official journal of the American Thyroid Association 09/2008; 18(9):967-71. · 2.60 Impact Factor -
Article: Immunopathogenesis of thyroid eye disease: emerging paradigms.
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ABSTRACT: Graves disease represents a systemic autoimmune process targeting the thyroid, orbit, and pretibial skin. The thyroid dysfunction is treatable, but no consistently effective medical therapy has yet been described for the orbital manifestations of Graves disease, also known as thyroid-associated ophthalmopathy or thyroid eye disease. Several autoantigens are potentially relevant to the pathogenesis of thyroid eye disease. Activating antibodies generated against the thyrotropin receptor can be detected in a majority of patients, and these drive hyperthyroidism. However, stimulating antibodies against the insulin-like growth factor-1 receptor (IGF-1R) may also play a role in the extra-thyroid manifestations of Graves disease. IGF-1R is overexpressed by orbital fibroblasts derived from patients with thyroid eye disease, whereas IGF-1R(+) T and IGF-1R(+) B cells are considerably more frequent in Graves disease. Actions of several cytokines and the molecular interplay peculiar to the orbit appear to provoke the inflammation, fat expansion, and deposition of excessive extracellular matrix molecules in thyroid eye disease. Based upon these new insights, several therapeutic strategies can now be proposed that, for the first time, might specifically interrupt its pathogenesis.Survey of Ophthalmology 55(3):215-26. · 2.35 Impact Factor