The ability of biomarkers to assess the severity of atopic dermatitis

Takeshi Nakahara; Daisuke Onozuka; Satoshi Nunomura; Hidehisa Saeki; Motoi Takenaka; Mai Matsumoto; Yoko Kataoka; Rai Fujimoto; Sakae Kaneko; Eishin Morita; Akio Tanaka; Ryo Saito; Tatsuro Okano; Tomomitsu Miyagaki; Natsuko Aoki; Kimiko Nakajima; Susumu Ichiyama; Makiko Kido-Nakahara; Kyoko Tonomura; Yukinobu Nakagawa; Risa Tamagawa-Mineoka; Koji Masuda; Takuya Takeichi; Masashi Akiyama; Yozo Ishiuji; Michie Katsuta; Yuki Kinoshita; Chiharu Tateishi; Aya Yamamoto; Akimichi Morita; Haruna Matsuda-Hirose; Yutaka Hatano; Hiroshi Kawasaki; Ayano Fukushima-Nomura; Mamitaro Ohtsuki; Koji Kamiya; Yudai Kabata; Riichiro Abe; Hiroshi Mitsui; Tatsuyoshi Kawamura; Gaku Tsuji; Norito Katoh; Masutaka Furue; Kenji Izuhara

doi:10.1016/j.jacig.2023.100175

The ability of biomarkers to assess the severity of atopic dermatitis

J Allergy Clin Immunol Glob. 2023 Sep 27;3(1):100175. doi: 10.1016/j.jacig.2023.100175. eCollection 2024 Feb.

Authors

Takeshi Nakahara¹, Daisuke Onozuka², Satoshi Nunomura³, Hidehisa Saeki⁴, Motoi Takenaka⁵, Mai Matsumoto⁵, Yoko Kataoka⁶, Rai Fujimoto⁶, Sakae Kaneko⁷, Eishin Morita⁷, Akio Tanaka⁸, Ryo Saito⁸, Tatsuro Okano⁹, Tomomitsu Miyagaki⁹, Natsuko Aoki¹⁰, Kimiko Nakajima¹⁰, Susumu Ichiyama⁴, Makiko Kido-Nakahara¹, Kyoko Tonomura¹¹, Yukinobu Nakagawa¹¹, Risa Tamagawa-Mineoka¹², Koji Masuda¹², Takuya Takeichi¹³, Masashi Akiyama¹³, Yozo Ishiuji¹⁴, Michie Katsuta¹⁴, Yuki Kinoshita¹⁵, Chiharu Tateishi¹⁵, Aya Yamamoto¹⁶, Akimichi Morita¹⁶, Haruna Matsuda-Hirose¹⁷, Yutaka Hatano¹⁷, Hiroshi Kawasaki¹⁸, Ayano Fukushima-Nomura¹⁸, Mamitaro Ohtsuki¹⁹, Koji Kamiya¹⁹, Yudai Kabata²⁰, Riichiro Abe²⁰, Hiroshi Mitsui²¹, Tatsuyoshi Kawamura²¹, Gaku Tsuji¹, Norito Katoh¹², Masutaka Furue¹, Kenji Izuhara³

Affiliations

¹ Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Oral Microbe Control, Graduate School of Medicine, Osaka University, Osaka, Japan.
³ Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
⁴ Department of Dermatology, Nippon Medical School, Tokyo, Japan.
⁵ Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
⁶ Department of Dermatology, Osaka Habikino Medical Center, Osaka, Japan.
⁷ Department of Dermatology, Shimane University Faculty of Medicine, Shimane, Japan.
⁸ Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁹ Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, Japan.
¹⁰ Department of Dermatology, Kochi Medical School, Kochi University, Kochi, Japan.
¹¹ Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹² Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹³ Department of Dermatology, Nagoya University Graduate School of Medicine, Aichi, Japan.
¹⁴ Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
¹⁵ Department of Dermatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹⁶ Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
¹⁷ Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan.
¹⁸ Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
¹⁹ Department of Dermatology, Jichi Medical University, Tochigi, Japan.
²⁰ Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
²¹ Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.

Abstract

Background: To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD.

Objective: The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD.

Methods: We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline.

Results: We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses.

Conclusion: We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.

Keywords: Atopic dermatitis; B-PAD; Biomarkers to Predict Clinical Improvement of AD in Patients Treated With Dupilumab; EASI; LDH; POEM; SCCA2; biomarker; eotaxin-3; precision medicine; pruritus-NRS.