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 HOLLAND, F. J. Articles by SAUNDERS, E. F. Search for Related Content PubMed PubMed Citation Articles by HOLLAND, F. J. Articles by SAUNDERS, E. F.

Concordant Graves' Disease after Bone Marrow Transplantation: Implications for Pathogenesis

Department of Pediatrics (F.J.H., E.F.S.) and Medicine (J.K.M., R.V.), University of Toronto, and the Hospital for Sick Children and the Wellesley Hospital Toronto, Ontario, Canada

Address all correspondence and requests for reprints to: Dr. F. J. Holland, Chairman Department of Pediatrics, Room 3N27, Faculty of Health Sciences, McMaster University, 1200 Main Street W, Hamilton, Ontario, Canada L8N 3Z5.

The current working hypothesis on the pathogenesis of autoimmune disease focuses on the interactions between susceptibility genes and environmental stimuli. In Graves' disease it is postulated that aberrant expression of HLA class II antigens on thyroid epithelial cells permits the presentation of specific thyroid antigen to activated lymphocytes. Evidence suggests that thyrocyte HLA-DR expression is secondary to the production of cytokines by presensitized T-lymphocytes.

A 20-yr-old woman and her 18-yr-old brother presented with classical findings of Graves' disease with ophthalmopathy within a year of each other. Diagnosis was confirmed by demonstration of elevated serum levels of T₄ and T₃, strongly positive titers of TSH binding inhibitory immunoglobulins, and histological examination after subtotal thyroidectomy. Eight years previously, acute life-threatening aplastic anemia in the brother led to therapeutic transplantation of bone marrow from his sister. After the procedure, 100% of his peripheral leucocytes were genotype 46,XX. HLA typing performed before transplantation and 2 months after thyroidectomy in the female indicated complete identity with her brother's leukocytes for class I and class II antigens. Thyroid autoantibodies at this time were weakly positive.

Although the concordance of thyroid disease in these patients could be due to chance, the patients were of different sexes, the family history was negative, and neither the probands nor the first degree relatives bore the HLA-DR3/B8 antigens. We propose that the male passively acquired a clone of programmed or activated lymphocytes from his sister and that his hyperthyroidism was not primarily dependent on exposure to specific thyroid-derived antigen. (J Clin Endocrinol Metab 72: 837–840, 1991)

Received July 30, 1990.

This article has been cited by other articles:

				Y Vardizer, A Lupetti, S Vandelanotte, A C Lankester, W M Wiersinga, and L Baldeschi Graves' orbitopathy in a patient with adrenoleukodystrophy after bone marrow transplantation Eur. J. Endocrinol., August 1, 2009; 161(2): 369 - 373. [Abstract] [Full Text] [PDF]

				T. Kushida, M. Inaba, K. Takeuchi, K. Sugiura, R. Ogawa, and S. Ikehara Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation Blood, March 1, 2000; 95(5): 1862 - 1868. [Abstract] [Full Text] [PDF]