JAK1 Gain-Of-Function Variant Causes Alopecia Areata, Atopic Dermatitis, And Autoimmune Thyroid Disease

    October 2025 in “ Journal of Allergy and Clinical Immunology ”
    S. Fujita, Shigenori Kabashima, Kumiko Yanagi, Kenji Toyokuni, Kazue Yoshida, Yumiko Miyaji, Shuji Takada, Kenichiro Motomura, Masato Tamari, Hisataka Nakazaki, Yoshitaka Hayashi, Naoko Nagano, Toru Uchiyama, Kimihiko Oishi, Susumu Yokoya, Takako Yoshioka, Kanako Tanase‐Nakao, Kiwako Yamamoto‐Hanada, Tatsuki Fukuie, Reiko Horikawa, Hirohisa Saito, Yoichi Matsubara, Yukihiro Ohya, Tadashi Kaname, Kenji Matsumoto, Hideaki Morita
    TLDR A JAK1 variant causes hair loss, skin issues, and thyroid disease, but treatment with a specific inhibitor can help.
    This study identifies a novel JAK1 gain-of-function (GOF) variant that causes alopecia areata (AA), atopic dermatitis (AD), and autoimmune thyroid disease (AITD) by predominantly enhancing IFN-γ signaling. The research involved a patient and his father, both exhibiting these conditions, and revealed a specific JAK1 variant not previously documented. Functional analysis showed that this variant robustly enhances IFN-γ signaling, which is crucial in AA. Treatment with the JAK1 inhibitor upadacitinib led to remission of AA in the patient and partial hair regrowth in the father. The findings suggest that JAK1 may be a common pathogenic link between AA, AD, and AITD, offering a potential therapeutic target. The study highlights the importance of understanding monogenic variants in inflammatory diseases to improve treatment strategies.
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