This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by HIROMATSU, Y. Articles by WALL, J. R. Search for Related Content PubMed PubMed Citation Articles by HIROMATSU, Y. Articles by WALL, J. R.

A Thyroid Cytotoxic Antibody That Cross-reacts With an Eye Muscle Cell Surface Antigen May Be the Cause of Thyroid-Associated Ophthalmopathy^*

Thyroid Research Unit, Montreal General Hospital Research Institute, and the Department of Medicine, McGill University Montreal, Quebec, Canada

Address all correspondence and requests for reprints to: Dr. J. R. Wall, Thyroid Research Unit, Department of Medicine, McGill University, Montreal General Hospital Research Institute, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.

A hitherto unrecognized thyroid antibody, which reacts with a thyroid cell surface antigen expressed on passaged thyroid cells, was identified in serum from patients with thyroidassociated ophthalmopathy using antibody-dependent cell-mediated cytotoxicity (ADCC) tests. The antibody was detected in 14 of 23 patients with Graves' hyperthyroidism (Gh) and associated ophthalmopathy, in 3 of 4 patients with Hashimoto's thyroiditis (HT) and ophthalmopathy, but in only 1 of 16 patients with Gh without clinically evident eye disease and 4 of 37 patients with HT without eye disease. The ADCC test also was positive in 2 of 30 patients with thyroid cancer, both of whom had had Gh and ophthalmopathy in the past. There was no correlation, in patients with ophthalmopathy, between the levels of the antibody (expressed as percent specific lysis) and the titers of antithyroid microsomal antibody measured using a hemagglutination assay. Based on the results of blocking experiments using mouse monoclonal antibodies against human thyroid peroxidase, now known to be the thyroid microsomal antigen, the corresponding antigen was not thyroid peroxidase. Moreover, the new antigen was expressed on cultured and passaged thyroid cells which do not express the microsomal antigen. In patients with ophthalmopathy there was a close correlation between the degree of lysis of passaged thyroid cells and that of eye muscle cells, and ADCC activity against passaged thyroid cells was absorbed by preincubation of positive serum samples with eye muscle and thyroid cell, but not other cell, monolayers. The reaction of a newly identified cytotoxic thyroid antibody with a shared epitope on eye muscle cells thus appears to be a possible mechanism for the development of ophthalmopathy in patients with Gh and, less often, HT

^* This work was supported by Grant MA698 from the MRC (Canada) and NIH Grant EY-05062-A3 of the National Eye Institute.

Received February 18, 1988.

This article has been cited by other articles:

				Y. Hiromatsu, T. Hoshino, H. Yagita, M. Koga, S. Sakisaka, J. Honda, D. Yang, N. Kayagaki, K. Okumura, and K. Nonaka Functional Fas Ligand Expression in Thyrocytes from Patients with Graves' Disease J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2896 - 2902. [Abstract] [Full Text]

				Y. Hiromatsu, D. Yang, I. Miyake, M. Koga, J. Kameo, M. Sato, Y. Inoue, and K. Nonaka Nicotinamide Decreases Cytokine-Induced Activation of Orbital Fibroblasts from Patients with Thyroid-Associated Ophthalmopathy J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 121 - 124. [Abstract] [Full Text]