IGG, IGA AND C3 DEPOSITS IN THE EXTRA-THYROIDAL MANIFESTATIONS OF AUTOIMMUNE GRAVES-DISEASE - THEIR IN-VITRO SOLUBILIZATION BY INTRAVENOUS IMMUNOGLOBULIN

Objective. To study the involvement of antibodies in the extrathyroida l manifestations of autoimmune Graves' disease, we determined the pres ence of IgG, IgA and IgM antibodies and C3c in connective tissue sampl es from patients with Graves' disease and pretibial myxedema (PTM) or thyroid associated ophthalmopathy (TAO). Methods. Connective orbital t issue samples were obtained from 12 patients undergoing orbital decomp ression for TAO, and skin samples from lesions on the pretibial area w ere obtained in 7 patients with PTM. Sections from each tissue sample were stained with fluorescin-isothiocianate conjugated anti-human IgG, IgA, IgM and C3c and were examined by a fluorescence optical instrume nt Other serial sections from each sample were incubated with human Ig G solutions (concentration 6 mg/ml or 20 mg/ml), human albumin (40 mg/ ml), PBS, myoglobin (40 mg/ml), or IgA (20 mg/ml), and were then proce ssed by a standard direct immunofluorescence staining procedure. Resul ts. Among the samples from TAO patients 8/12 (67%) were positive for I gG deposition, 4/9 (44%) were positive for IgA, 1/9 (11%) was positive for IgM and 4/9 (44%) were positive for C3c deposition. Orbital conne ctive samples from 3 non-TAO patients were all negative. Among samples from PTM patients 4/7 (57%) were positive for IgG deposition, 3/4 (75 %) were positive for IgA, 0/4 was positive for IgM and 3/7 (43%) were positive for C3c deposition. Skin samples from 5 control patients unde rgoing skin biopsy for non-autoimmune diseases were all negative. Incu bation with human IgG (20 mg/ml) resulted in the complete disappearanc e of IgG and C3c deposition in all positive patients. No significant v ariation in IgG fluorescent staining after incubation with either 6 mg /ml of IgG solution, human albumin, PBS, myoglobin or IgA was observed . Conclusion. The results of our study suggest that different classes of antibodies, mainly IgG and IgA, may be implicated in the disease pr ocess in autoimmune TAO and PTM. Activation of the complement cascade, via the classic or the alternative pathway, could take place in about 40% of these patients. IVIG in vitro may solubilize, by a specific me chanism, IgG and complement immune complex deposition in the extrathyr oidal manifestations of autoimmune Grave's disease.