ANALYSIS OF FIBROBLAST-STIMULATING ACTIVITY IN IGG FROM PATIENTS WITHGRAVES DERMOPATHY

Conflicting results have been reported on the effect of IgGs from pati ents with Graves' dermopathy on dermal fibroblast function. We have an alyzed 14 dermopathy IgGs prepared by protein G affinity chromatograph y. These caused FRTL-5 thyroid cells to synthesize significantly great er amounts of glycosaminoglycans (GAG) and protein than IgGs from norm al controls (p < 0.05). [H-3]Thymidine incorporation was also signific antly increased (p < 0.05) and there was a significant correlation bet ween all three parameters and the ability of these IgGs to stimulate i odide incorporation (p < 0.001). Dermopathy and control IgGs caused a modest increase in GAG synthesis by dermal fibroblasts but there was n o signiricant difference between the two types of IgG. Increased GAG p roduction was detectable in both culture medium and the extracellular matrix, and there was no difference between fibroblasts derived from t he arm and leg. Conditioned medium from thyroid cells treated with der mopathy or control IgGs caused a greater increase in GAG production th an the IgGs alone, but again there was no difference between the two s ources of IgG. Neither control nor dermopathy IgG affected fibroblast protein synthesis or [H-3]thymidine incorporation. Our results argue a gainst 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 diso rder.