Soluble CTLA-4 is increased in Graves disease and not related to thyroid status or ophthalmopathy severity
Jacek Daroszewski1, Edyta Pawlak2, Marek Bolanowski1, Miroslaw Slowik3 & Irena Frydecka4
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a B7-binding protein that plays an important role in the down-regulation of T-cell activation. CTLA-4 function is closely associated with predisposition to autoimmune diseases. A native soluble form of CTLA-4 (sCTLA-4) is reported to be present in the sera of patients suffering from autoimmune thyroid disease. In this study we report data on sCTLA-4 concentrations in patients with clinical expression of Graves disease.
The study group consisted of 102 patients with Graves disease (83 females and 19 males, mean age: 50±11 years). Of these, 47 were euthyroid, 38 were hyper-, and 9 were hypothyroid. Nine patients were without clinical signs and symptoms of ophthalmopathy, while 42 presented mild and 51 severe ophthalmopathy. The control group was 38 apparently healthy volunteers. Study was approved by a local Ethical Committee.
Soluble CTLA-4 was measured in serum by means of ELISA.
sCTLA-4 was not measurable in 13 samples from the control group, while it could be estimated in all the patient serum samples and was higher than in control group (range: 0.02-1983.94 ng/ml, median: 7.48 ng/ml, dispersion: 11.2 ng/ml vs. range: 0.16-35.49 ng/ml, median: 3.2 ng/ml, dispersion: 3.98 ng/ml, respectively, P=0.03).
Soluble CTLA-4 concentration was not related to FT4 or to FT3 level (r=0.026 and r=−0.034, respectively). Regression analysis of factors describing the severity of the course of disease (thyroidectomy, 131I treatment, or methylprednisolone treatment in the past) did not reveal any link with sCTLA-4 concentration (P=0.15). Soluble CTLA-4 serum level was also not related to the severity of ophthalmopathy.
In our group of 102 patients with Graves disease, sCTLA-4 was higher than in the control subjects. Soluble CTLA-4 was a sensitive marker of the disease and appeared to be related neither to metabolic status nor to clinical course of the disease or the severity of eye changes.