Study explains why Graves’ disease also targets eye’s orbit

A cell type that causes significant scarring in lung disease appears to have a similar effect in Graves’ disease. The cells, called fibrocytes, are present at a higher than normal frequency in patients with Graves’ disease, according to a new study, the first to associate fibrocytes with this autoimmune disease.

The discovery is a major step forward in explaining how and why the orbit of the eye is subject to scarring and inflammation in Graves’ disease.

The findings also may lead to new treatment strategies to target scarring or fibrosis, say authors Dr. Raymond Douglas and Dr. Terry J. Smith, specialists in Graves’ disease at the Kellogg Eye Center. The study appears in the January issue of the Journal of Clinical Endocrinology & Metabolism.

Graves’ disease is an autoimmune disorder that results in an overactive thyroid. Up to half of those affected by the disease will develop inflammation or fibrosis around their eyes, creating the bulging appearance associated with Graves’ eye disease, also called thyroid-associated ophthalmopathy. Excessive scarring can cause such manifestations as double vision or even loss of vision.

“Today we have medications to reduce inflammation, but these drugs typically do not treat the fibrotic effects of thyroid eye disease,” says Douglas, an oculoplastics surgeon. “Our study is the first to implicate fibrocytes in the disease process, a finding that should open up new possibilities for treatment.”

Fibrocytes are immune cells derived from bone marrow that circulate through the bloodstream. They can infiltrate tissue, like the lungs, kidney and liver, generating excess connective tissue and areas of fibrosis, for example, following pulmonary or kidney injury.

To determine whether fibrocytes play a similar role in Graves’ disease, these investigators and their colleagues examined tissue samples from 70 patients with the disease and compared them to 25 healthy subjects. The samples were gathered while Smith and Douglas were on the faculty of the University of California at Los Angeles. They found that fibrocytes were present at substantially higher frequencies — as much as five times greater — in patients with Graves’ disease. These levels were observed in both the bloodstream and in the orbital tissues of patients who had developed thyroid eye disease.

As follow-up to the study, the Kellogg researchers plan to more fully identify the role of fibrocytes in the disease process and test whether several new agents, such as rituximab, can reduce these cells as they circulate through the bloodstream. The authors also recently demonstrated that rituximab was highly effective in treating patients with severe Graves’ disease.

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