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

Abstract

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.

Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation

“…Post-HSCT AITD was first reported in 1987, 16 and a total 17 cases have since been reported (Table 3). [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] They included five cases of hypothyroidism and 12 cases of thyrotoxicosis. The male to female ratio in HSCT recipients was roughly equal (1.83:1), but similar to our experience, donors were markedly skewed to females (0.23:1).…”

Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation

“…[7][8][9][10][11][12] However, such adoptive transfer is a minor component of the many etiologies. Most cases of post-BMT autoimmunity are known to result from an immunologic dysregulation ('immunologic chaos').…”

“…13 There have been several cases where AITD developed after BMT. [7][8][9][10][11][12] In particular, post-transplant adoptive hyperthyroidism is rarer than adoptive hypothyroidism, and in total, eight case reports have been published including the latest one by Berisso et al 12 However, to our knowledge, no cases have been described in which a pre-existing AITD disappeared following BMT with the exception of one case of Graves' disease which remitted. 4 Remission of previous, clinically unidentified AITDs may have occurred more frequently than was found in this study.…”

Prevention of autoimmune hearing loss in MRL/lpr mice by bone marrow transplantation

“…In humans, it has been reported that autoimmune diseases such as autoimmune thyroiditis, [38][39][40] Graves' disease, 41 insulin-dependent diabetes mellitus 42,43 and myasthenia gravis 44,45 are transferred to recipients after BMT. It has also been reported that autoimmune diseases such as psoriasis vulgaris, 46,47 ulcerative colitis 46 and palmoplantar pustular psoriasis 40 are resolved after BMT in patients suffering from both leukemia and autoimmune diseases.…”