Immunoglobulin (Ig)G from patients with Grave's disease (GD) can activate thyrocytes to express powerful T-cell chemoattractants, say US scientists who suggest that this mechanism may be key for lymphocyte recruitment to the thyroid in sufferers of the disorder.
The researchers found that the expression of the chemoattractants interleukin (IL)-16 and RANTES (regulated upon activation, normal T cell expressed and secreted) was provoked when the insulin-like growth factor (IGF)-receptor of thyrocytes was activated by IgG taken from patients with GD (GD-IgG).
Interestingly, they did not find any evidence to suggest that thyroid-stimulating hormone (TSH) was involved in the attraction of IL-16 or RANTES.
Explaining the background to their study in the journal Endocrinology, the authors write: "Currently, little is known about the chemoattractant molecules expressed in the thyroid, the identity of resident thyroid cells expressing them, or the mechanisms through which their production is up-regulated."
It is particularly important to understand these mechanisms in autoimmune conditions such as GD, where the thyroid becomes infiltrated with lymphocytes, they emphasize.
Terry Smith, from the University of California Los Angeles Medical Center, and colleagues therefore examined chemoattractant activity elicited by thyrocytes in response to GD-IgG samples taken from five different patients with GD and IgGs taken from a healthy control individual without GD.
Thyrocytes were obtained from patients who underwent thyroidectomy as part of treatment for a variety of conditions including GD and multinodular goiter.
Results revealed that all five samples of GD-IgG increased total chemotactic activity that was attributable to IL-16 and RANTES in thyrocytes, with responses ranging from 171% to 376% above those observed for control cells.
Of note, TSH failed to stimulate any chemotactic activity in thyrocytes.
"Our findings suggest that thyrocytes can be activated by GD-IgG and IGF-I to express powerful T-cell chemoattractants. These actions of GD-IgG appear to be mediated through pathways independent of the TSH receptor," the researchers summarize.
"The IGF-IR pathway represents a potentially attractive therapeutic target, the interruption of which might ameliorate autoimmune thyroid disease," they conclude.