Thymomas, a rare type of cancer in the thymus gland, can result in a newly described autoimmune disease, potentially leading to hypopituitarism, according to a recent study in Scientific Reports. Understanding the underlying mechanisms could improve understanding and development of treatment for similar autoimmune diseases.1
The pituitary gland, located at the base of the brain, regulates different hormones. Previous research revealed an autoimmune condition caused by autoimmunity against PIT-1, a pituitary-specific transcription factor.
PIT-1 plays an essential role in the generation of growth hormone, thyroid-stimulating hormone, and prolactin. Anti-PIT-1 antibodies in the serum of patients with this newly described disease resulted in naming it anti-PIT-1 antibody syndrome. The etiology of this disease, however, remained unclear.
Here, the researchers revealed that thymoma was present in every patient presenting with anti-PIT-1 antibody syndrome. Additionally, researchers discovered increased expression of PIT-1 in neoplastic cortical thymic epithelial cells.
Researchers also detected PIT-1-reactive cytotoxic T cells in these 3 patients. Cytotoxic T cells are a type of white blood cell that attacks tumor cells as part of the immune response. They are refined for their roles in the thymus, undergoing positive and negative selections.
These T cells are selected to recognize antigens in the thymic cortex in positive selection and selected out if they respond to self-antigens in the medulla in negative selection. Ideally, T cells only target exogenous antigens.
In anti-PIT-1 antibody syndrome, PIT-1 expression in the thymoma results in T cells recognizing endogenous PIT-1 as exogenous, thus triggering autoimmunity.
“[Approximately] 20% of hypopituitarism cases are caused by unknown factors. This discovery has clarified one of the causes,” explained Yutaka Takahashi, MD, PhD, associate professor in the Department of General Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
1. Bando H, Iguchi G, Okimura Y, et al. A novel thymoma-associated autoimmune disease: anti-PIT-1 antibody syndrome. Sci Rep. 2017 Feb 20. doi: 10.1038/srep43060 [Epub ahead of print]