Analysis of fibroblast-stimulating activity in IgG from patients with Graves' dermopathy.
Conflicting results have been reported on the effect of IgGs from patients with Graves' dermopathy on dermal fibroblast function. We have analyzed 14 dermopathy IgGs prepared by protein G affinity chromatography. These caused FRTL-5 thyroid cells to synthesize significantly greater amounts of glycosaminoglycans (GAG) and protein than IgGs from normal controls (p < 0.05). [3H]Thymidine incorporation was also significantly increased (p < 0.05) and there was a significant correlation between all three parameters and the ability of these IgGs to stimulate iodide incorporation (p < 0.001). Dermopathy and control IgGs caused a modest increase in GAG synthesis by dermal fibroblasts but there was no significant difference between the two types of IgG. Increased GAG production was detectable in both culture medium and the extracellular matrix, and there was no difference between fibroblasts derived from the arm and leg. Conditioned medium from thyroid cells treated with dermopathy or control IgGs caused a greater increase in GAG production than the IgGs alone, but again there was no difference between the two sources of IgG. Neither control nor dermopathy IgG affected fibroblast protein synthesis or [3H]thymidine incorporation. Our results argue against a role for circulating IgGs in mediating Graves' dermopathy and make it unlikely that the TSH receptor antibodies are acting directly on a functional receptor expressed by dermal fibroblasts in this disorder.
Metcalfe
R A
RA
Department of Medicine, University of Sheffield Clinical Sciences Centre, United Kingdom.
Davies
R
R
Weetman
A P
AP
D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006111:Graves Disease / Q000097:blood / Q000150:complications* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology*; D012016:Reference Values; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012871:Skin Diseases / Q000097:blood / Q000209:etiology / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D006025:Glycosaminoglycans; D007074:Immunoglobulin G; D004247:DNA; D005944:Glucosamine; D013936:Thymidine