Article Source: Kobe University

Abstract:

Thymomas, a type of tumor originating from thymic gland triggers a newly-identified autoimmune endocrine disease that leads to hypopituitarism, a research group has found. The underlying mechanisms behind this could help to understand and develop a treatment for similar autoimmune diseases.

Complete Article:

Thymomas is a type of type of tumor which originates from the epithelial cells of the thymus. Scientists from Kobe University have recently found that thymomas trigger an autoimmune endocrine disease which leads to hypopituitarism. Researchers say that the hidden mechanisms behind this might prove to be beneficial in better understanding and developing a treatment for similar autoimmune diseases.

 Associate Professor TAKAHASHI Yutaka, Research Fellow BANDO Hironori, and Associate Professor IGUCHI Genzo in Kobe University Graduate School of Medicine led the research group.

Autoimmune diseases occur when our own immune system that defends the body against foreign elements starts attacking its own cells and tissues of the body. This result from the activation of self-reactive T and B cells on stimulation by different types of triggers. Autoimmune disease can be of various types including rheumatoid arthritis (which affects roughly 1% of the population), systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, etc.

The pituitary gland often referred to as the master gland of the body is located at the base of the brain and plays a central role in regulating various hormones. During the previous studies, Professor Takahashi’s research team discovered a new clinical entity caused by autoimmunity against PIT-1, a pituitary-specific transcription factor that plays an essential role in producing growth hormone (GH), thyroid stimulation hormone (TSH), and prolactin (PRL). Because anti-PIT-1 antibodies were detected in patients with this disease, the group named this disease anti-PIT-1 antibody syndrome. However, it remained unclear why the breakdown of immune tolerance against PIT-1 occurred.

While, in the new study, the team discovered that a thymoma was detected in every case of anti-PIT-1 antibody syndrome. PIT-1 was abnormally expressed within the thymoma and this evoked the immune tolerance breakdown.

Cytotoxic T cells (CTLs) also frequently referred to as killer T-cell are a type of white blood cell whose principal function is to kill cells that have been infected by bacteria and viruses. They are also involved in destroying tumor cells as a part of immune responses. These cells are “trained” in the thymic gland, and during these processes both positive and negative selections take place. In the thymic cortex, T cells are trained to be able to recognize various antigens (positive selection) and in the medulla, T cells that react with self-antigens are deleted (negative selection). These sophisticated systems enable T cells to correctly target foreign antigens. However, in anti-PIT-1 antibody syndrome, PIT-1 is abnormally expressed in thymoma cells, therefore T cells that react to PIT-1 are produced and an autoimmunity is triggered.

In the context of this research, Associate Professor Takahashi says, “Around 20% of hypopituitarism cases are caused by unknown factors. This discovery has clarified one of the causes. We hope that this discovery will contribute to more effective diagnosis and treatment for patients suffering from autoimmune pituitary diseases, hypopituitarism, and thymomas.”

These findings of this research have been published in the online edition of Scientific Reports.

Journal Reference:

Hironori Bando, Genzo Iguchi, Yasuhiko Okimura, Yukiko Odake, Kenichi Yoshida, Ryusaku Matsumoto, Kentaro Suda, Hitoshi Nishizawa, Hidenori Fukuoka, Atsuko Mokubo, Katsuyoshi Tojo, Yoshimasa Maniwa, Wataru Ogawa, Yutaka Takahashi. A novel thymoma-associated autoimmune disease: Anti-PIT-1 antibody syndromeScientific Reports, 2017; 7: 43060 DOI: 10.1038/srep43060