Appearance of Thyroid Stimulating and Blocking Immunoglobulins after Bone Marrow Transplantation: Presentation of Two Contrasting Cases

Abstract

Two acute leukemia cases who presented autoimmune thyroid diseases after bone marrow transplantation (BMT) are described with reference to the pathogenesis of their autoimmune clones. A 37-year old Japanese woman developed Graves' hyperthyroidism 39 months after allogeneic BMT for acute myeloid leukemia (AML) donated from her sister. Although both donor and recipient were euthyroid and negative for thyroid autoimmunity before BMT, the donor was positive for anti-nuclear and anti-single strand DNA autoantibodies. Studies on polymorphism for variable number of tandem repeat region of T-cell receptor gene suggested that the lymphocytes responsible for the hyperthyroidism were of donor origin. The second case was a 12-year-old Japanese schoolboy who presented nongoitrous hypothyroidism 2 years after autologous BMT for acute lymphoblastic leukemia (ALL). He had been clinically euthyroid before transplantation. Family history revealed that his mother and sister had a history of Graves' disease. His serum was positive for thyroid-stimulation blocking antibody. It is highly likely that the autoimmune process was activated after transient immune suppression during peri-BMT period in this patient. Pathogenesis, incidence, and observed time lag between BMT and development of autoimmune thyroid diseases were discussed.

Profound Reduction in T-helper (Th) 1 lymphocytes in Peripheral Blood from Patients with Concurrent Type 1 Diabetes and Graves' Disease

“…These results suggest that Th1-associated T lymphocytes in peripheral blood were profoundly reduced in patients who had both diseases, compared with either disease alone. Since the pathogenesis of Graves' disease is linked to production of thyrotropin (TSH) receptor antibodies (TRAb) that stimulates the thyroid follicular cell TSH receptor, humoral immunity plays a crucial role in the pathogenesis of Graves' disease [9,10,12,13]. However, a recent study demonstrated the recruitment of CXCR3-expressing Th1 lymphocytes in the thyroid glands of patients at the initial phase of Graves' disease [14], suggesting Th1 dominance within the thyroid gland, rather than Th2, at the onset of illness.…”

Salivary evaluation of pediatric patients with cancer, before and after antineoplasic treatment

“…Cancer and anticancer therapies are known to compromise endocrine functions in children (10,13), as observed for thyroid function in the present study. Tumor development can interrupt thyroid regulation and persistence of this stimulus results in the disordered production of its hormones (15) or of TSH receptor autoantibodies (16,17).…”

Immune-Mediated Complications after Hematopoietic Stem Cell Transplantation

“…A single-center retrospective study in China in allogeneic and autologous HSCT patients theorized HLA-related AITD, although female donor, inherent patient susceptibility, conditioning regimen, and GVHD were associated with development of AITD [12]. There are several case reports suggesting that transfer of autoantibodies along with donor lymphocytes can cause AITD after HSCT; however, in many cases, donors never had clinical or laboratory evidence of thyroid dysfunction [26,68,71,74]. Although the etiology is uncertain, the onset of clinical symptoms can be delayed several years and presentation can be rapid, requiring regular monitoring of thyroid function for early diagnosis and initiation of treatment.…”