Enhancement of soluble CD28 levels in the serum of Graves' disease.

Graves' disease is an autoimmune disease of the thyroid gland mediated by T cells. CD28, a member of costimulatory molecules, plays a pivotal role in regulating T-cell responses. Plasma-soluble CD28 is one form of CD28 in peripheral blood. To investigate the concentrations of soluble CD28 in patients with Graves' disease, we used a sensitive dual monoclonal antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect the soluble form of CD28. Our results suggested that mean concentrations of soluble CD28 in plasma of patients with Graves' disease were 1.79 ±1.52 ng/ml, and levels of soluble CD28 in healthy subjects were only 0.83 ±1.35 ng/ml. Concentrations of soluble CD28 detected in patients with Graves' disease were significantly higher than those of healthy subjects (p < 0.01). Moreover, there was a significant positive correlation between the concentrations of soluble CD28 in plasma and levels of FT3 (r = 0.663), FT4 (r = 0.624) and TRAb (r = 0.728) in serum, but a negative correlation was found between sCD28 levels and TSH (r = -0.726). Through in vitro experiments we observed that engagement of soluble CD28 protein and B7-1/B7-2 molecules expressed on dendritic cells could exert the secretion of cytokine IL-6, which may promote the production of autoantibody and aggravate Graves' disease. Therefore, aberrant elevation of plasma-soluble CD28 in patients with Graves' disease may reflect the dysregulation of immune system, and may serve as a useful biomarker in Graves' disease diagnosis.