Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture

Abstract

Hyaluronic acid and proteoglycan accumulate in the affected skin of Graves' disease patients with pretibial myxedema (PTM). We aimed to determine whether an autoantibody IgG circulating in PTM patients stimulates proteoglycan synthesis in human skin fibroblasts, resulting in PTM. IgGs were purified from 14 normal subjects, 11 Graves' disease patients with PTM, 5 Graves' disease patients with active ophthalmopathy and 15 Graves' disease patients with neither PTM nor ophthalmopathy. Human skin fibroblasts were incubated with the IgGs and labeled with [35S]sulfate. The medium and cell layer were separated and the proteoglycan was extracted. The 35S radioactivity in the proteoglycan fraction was measured. Compared with normal IgGs or with those of Graves' disease without PTM or ophthalmopathy, PTM IgGs significantly increased the incorporation of the 35S into the proteoglycan. The effect of PTM IgG was dose-dependent. As PTM IgG did not alter degradation of the 35S labeled proteoglycan, an increase in 35S incorporation reflects increased synthesis. The effect was mediated through a mechanism other than adenylate cyclase activation. The present study demonstrates the presence of an autoantibody in PTM IgG that stimulates proteoglycan production through human skin fibroblasts. This is not correlated with the thyroid stimulating antibody activity. It is suggested that the activity of this antibody leads to the development of PTM.