Autoimmune Disease Trigger Associated with Thymoma Tumors

By LabMedica International staff writers
Posted on 16 Mar 2017
Researchers have discovered that a newly-identified autoimmune endocrine disease – “Anti-PIT-1 antibody syndrome” – that leads to hypopituitarism is likely caused by overexpression of PIT-1 in the thymoma type of tumor originating from the thymic gland.

The study was led by associate Prof. Yutaka Takahashi, research fellow Hironori Bando, and associate Prof. Genzo Iguchi of Kobe University Graduate School of Medicine, Japan. The pituitary gland plays a central role in regulating various hormones. In previous studies, Prof. Takahashi’s research team discovered a new clinical entity caused by autoimmunity against PIT-1, a critical pituitary-specific transcription factor. Because anti-PIT-1 antibodies were detected in patients with this disease, the group named it anti-PIT-1 antibody syndrome. However, it remained unclear why the breakdown of immune tolerance against PIT-1 occurred.

Image: The pituitary-specific transcription factor PIT-1 plays an essential role in producing growth hormone (GH), thyroid stimulation hormone (TSH), and prolactin (PRL). Researchers have discovered that a thymoma was detected in examined cases of “anti-PIT-1 antibody syndrome”. PIT-1 expression was abnormally increased within the thymoma and this likely evoked the immune tolerance breakdown and hypopituitarism that occurs in patients with this autoimmune disorder (Photo courtesy of Kobe University).

In this new study, the team discovered that a thymoma was detected in examined cases of anti-PIT-1 antibody syndrome. Cytotoxic T cells can destroy tumor cells as a part of immune responses. 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). However, in anti-PIT-1 antibody syndrome, PIT-1 expression is abnormally increased in thymoma cells, therefore T cells that react to PIT-1 are produced and an autoimmunity is triggered, evoking the immune tolerance breakdown in the patients.

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

The study, by Bando H et al, was published online February 20, 2017, in the journal Scientific Reports.


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