Clinical characteristics and treatment strategies for A20 haploinsufficiency in Japan: a national epidemiological survey

Clinical characteristics and treatment strategies for A20 haploinsufficiency in Japan: a national epidemiological survey

BackgroundThe severity of A20 haploinsufficiency (HA20) varies, with no established clinical guidelines for treatment. This study aimed to elucidate the clinical characteristics of, and the efficacy of treatments attempted in, patients with HA20 in Japan.MethodsClinical information on HA20 patients...

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Main Authors: Mayuka Shiraki, Saori Kadowaki, Yuki Miwa, Kenichi Nishimura, Yuta Maruyama, Dai Kishida, Kazuo Imagawa, Chie Kobayashi, Hidetoshi Takada, Kanako Mitsunaga, Yuzaburo Inoue, Takasuke Ebato, Takayuki Miyamoto, Eitaro Hiejima, Shuzo Sato, Kiyoshi Migita, Tadashi Matsubayashi, Daisuke Kobayashi, Eriko Hasegawa, Utako Kaneko, Takashi Ishikawa, Masafumi Onodera, Kohei Matsushita, Yuhki Koike, Hiroaki Umebayashi, Fumihiko Kakuta, Daiki Abukawa, Yasutomo Funakoshi, Masataka Ishimura, Yusuke Otani, Takuya Nishizawa, Takashi Ishige, Reiko Hatori, Seiji Tanaka, Shouichirou Kusunoki, Kimitoshi Nakamura, Harumi Shirai, Yoshiho Hatai, Futaba Miyaoka, Shuya Kaneko, Asami Shimbo, Masaki Shimizu, Hirokazu Kanegane, Motomu Hashimoto, Nobuo Negoro, Taro Yoshida, Yasunori Wada, Masaaki Usami, Taizo Wada, Kazushi Izawa, Takahiro Yasumi, Ryuta Nishikomori, Hidenori Ohnishi
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
Subjects:
A20 haploinsufficiency
TNFAIP3
autoinflammatory disease
molecular target drugs
secondary failure
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548042/full
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Summary:BackgroundThe severity of A20 haploinsufficiency (HA20) varies, with no established clinical guidelines for treatment. This study aimed to elucidate the clinical characteristics of, and the efficacy of treatments attempted in, patients with HA20 in Japan.MethodsClinical information on HA20 patients from medical records was retrospectively collected through the attending physicians.ResultsSeventy-two HA20 patients were identified in Japan. And, 54 patients from 37 unrelated families were analyzed in detail. HA20 patients exhibited common features, including recurrent fever, gastrointestinal and musculoskeletal symptoms, and autoimmune disease; various organ disorders (e.g. neurological, liver, and pulmonary diseases) were less common complications. Molecular target drugs (MTDs) were administered in 44.4% of patients, among which anti-tumor necrosis factor (TNF)-α agents showed efficacy in 59.5% of patients. Eleven patients did not experience control of inflammation with initial MTDs, most commonly because of relapse due to secondary failure of MTDs. Anti-drug antibodies were related to the secondary failure of adalimumab in one patient and infusion reactions to infliximab in two patients. In such refractory cases, other treatments (e.g. switching the first MTD to an alternative agent or adding a Janus kinase inhibitor or immunomodulators, or allogeneic hematopoietic cell transplantation [HCT]) were attempted.ConclusionsOur survey revealed that anti-TNF-α agents showed high efficacy. However, secondary failure of MTDs was a significant refractory-related factor in HA20 patients in Japan. Although anti-interferon therapies, thalidomide, and HCT might be potential treatment options, the results of this study suggest that further research is necessary to establish suitable treatments for HA20, especially for those with refractory disease.
ISSN:1664-3224

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