Faculty Profiles - TAKEICHI Takuya

Increased JAK activation in cutaneous vasculitis. Reviewed International journal

Aoi Ebata, Mariko Ogawa-Momohara, Ryo Fukaura, Yuta Yamashita, Haruka Koizumi, Takuya Takeichi, Yoshinao Muro, Masashi Akiyama

Journal of the American Academy of Dermatology Vol. 90 ( 3 ) page： 627 - 629 2024.3

Dual clinical features of fine and rough scales seen in a combined ichthyosis vulgaris and X-linked recessive ichthyosis patient with atopic dermatitis. Reviewed International journal

Yoshimasa Nakane, Takenori Yoshikawa, Takuya Takeichi, Michihiro Kono, Masashi Akiyama

The Journal of dermatology Vol. 51 ( 2 ) page： e49 - e50 2024.2

The ability of biomarkers to assess the severity of atopic dermatitis. Reviewed International journal

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

The journal of allergy and clinical immunology. Global Vol. 3 ( 1 ) page： 100175 - 100175 2024.2

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.jacig.2023.100175

Cross-sectional nationwide epidemiologic survey on quality of life and treatment efficacy in Japanese patients with congenital ichthyoses. Reviewed International journal

Yuika Suzuki, Kana Tanahashi, Chiaki Terashima-Murase, Takuya Takeichi, Yumiko Kobayashi, Fumie Kinoshita, Masashi Akiyama

Journal of dermatological science Vol. 113 ( 1 ) page： 2 - 9 2024.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Congenital ichthyoses sometimes present with severe skin symptoms that significantly affect the patient's quality of life (QOL). Symptomatic treatments are the mainstay therapies, and their efficacy is limited and inadequate. OBJECTIVE: To assess the disease severity and QOL in patients with congenital ichthyoses, and to investigate the effectiveness of current treatments. METHODS: We conducted a questionnaire-based Japan-wide epidemiological survey of patients with congenital ichthyosis who received medical care from 1 January 2016-31 December 2020. Effectiveness of past and current treatments was assessed. The outcomes were the physician's assessment, disease severity assessed using the clinical ichthyosis score (CIS), and the disease burden estimated using the Dermatology Life Quality Index (DLQI), the Children's Dermatology Life Quality Index (CDLQI), and the Infants' Dermatitis Quality of Life Index. RESULTS: One hundred patients with 14 ichthyosis subtypes from 47 institutes were included in the final analysis. The CDLQI score showed a positive correlation with CIS (rs = 0.59, p = 0.004), while the DLQI score showed no significant correlation (rs = 0.13, p = 0.33). All existing medications were effective for many patients. Etretinate improved QOL and reduced CIS, but side effects including bone growth retardation were reported. Decreased treatment willingness was observed in patients with very low and very high CIS. CONCLUSION: QOL scores were found to correlate with CIS in children, but not in adults. Considering the adverse events, it is speculated that etretinate is not indicated for children with mild cases. Petrolatum was the most commonly used medication, even in patients who were reluctant to receive treatment.

DOI： 10.1016/j.jdermsci.2023.11.002

Patients with keratinization disorders due to ABCA12 variants showing pityriasis rubra pilaris phenotypes. Reviewed International journal

Takuya Takeichi, Takahiro Hamada, Mayuko Yamamoto, Yasutoshi Ito, Aya Kawaguchi, Haruka Kobashi, Takenori Yoshikawa, Hiroshi Koga, Norito Ishii, Takekuni Nakama, Yoshinao Muro, Tomoo Ogi, Masashi Akiyama

The Journal of dermatology Vol. 51 ( 1 ) page： 101 - 105 2024.1

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Pathogenic variants in ABCA12 are important causative genetic defects for autosomal recessive congenital ichthyoses (ARCI), which include congenital ichthyosiform erythroderma (CIE), harlequin ichthyosis, and lamellar ichthyosis. In addition, pathogenic variants in ABCA12 are known to cause a localized nevoid form of CIE due to recessive mosaicism. We previously reported siblings who carried an ABCA12 variant but did not show a "congenital" phenotype. They were considered to have pityriasis rubra pilaris (PRP). Here, we present a further patient with ABCA12 variants whose phenotype was not congenital ichthyosis, in an independent family. Notably, these three patients had geographic unaffected areas. Such areas are not usually found in patients with ARCI who have ABCA12 variants, suggesting mild phenotypes for these patients. Interestingly, the histological features of the ichthyotic lesions in these patients resembled those of PRP. All three patients had homozygous pathogenic missense variants in ABCA12. Our findings expand the phenotypic spectrum of patients with ABCA12 variants.

DOI： 10.1111/1346-8138.16967

Generalized pustular psoriasis that developed in a patient with an NFKB2 variant. Reviewed International journal

Shogo Wada, Takeshi Namiki, Aoi Ebata, Takuya Takeichi, Masashi Akiyama, Masafumi Yamada, Atsushi Hijikata, Yutaka Shimomura, Hirokazu Kanegane, Naoko Okiyama

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG Vol. 22 ( 1 ) page： 118 - 120 2023.12

Lysophospholipase D from Thermocrispum limits psoriatic inflammation by hydrolyzing epidermal lysoplasmalogen produced by group IIF secreted phospholipase A2. Reviewed International journal

Haruka Hakoi, Yoshimi Miki, Saki Nomura, Kimiko Nakajima, Chiaki Terashima-Murase, Takuya Takeichi, Shigetoshi Sano, Masashi Akiyama, Shin-Ichi Sakasegawa, Makoto Murakami, Kei Yamamoto

Biochimie Vol. 215 page： 75 - 87 2023.12

Language：English Publishing type：Research paper (scientific journal)

Epidermal lipids play important roles in skin homeostasis and diseases. Psoriasis is an inflammatory disease characterized by keratinocyte hyperproliferation and Th17 immune responses. We previously reported that ethanolamine-type lysoplasmalogen (P-LPE), preferentially produced by group IIF secreted PLA2 (sPLA2-IIF/PLA2G2F) that is expressed in the suprabasal epidermis, promotes epidermal hyperplasia in psoriatic inflammation. Herein, we show that forcible degradation of epidermal P-LPE by topical application of recombinant lysophospholipase D (LyPls-PLD) from Thermocrispum, a lysoplasmalogen-specific hydrolase, attenuated epidermal hyperplasia and inflammation in imiquimod-induced and K5.Stat3C-transgenic mouse psoriasis models. In humans, P-LPE levels were elevated in the tape-stripped stratum corneum of patients with psoriasis. Moreover, in primary cultured human epidermal keratinocytes, aberrant cell proliferation and activation by psoriatic cytokines were sPLA2-IIF/P-LPE-dependent and were suppressed by the addition of LyPls-PLD with a decrease in P-LPE. These findings confirm that the sPLA2-IIF/P-LPE axis in the epidermis indeed regulates psoriasis, that P-LPE is a lipid biomarker that predicts the severity of psoriasis, and that pharmacological removal of this bioactive lipid is useful to prevent the disease. Thus, our study may lead to the development of drug discovery and diagnostic techniques based on this pathway.

DOI： 10.1016/j.biochi.2023.09.027

An in-frame 18 bp deletion in linker domain L1 of KRT9 identified in a Japanese patient with epidermolytic palmoplantar keratoderma. Reviewed International journal

Michiya Omi, Takuya Takeichi, Tomoko Chiba, Yoshihide Asano, Yoshinao Muro, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 11 ) page： E370 - E372 2023.11

Diagnosis of acute generalized pustular bacterid facilitated by point-of-care testing. Reviewed International journal

Ryo Fukaura, Chiaki Terashima-Murase, Kana Tanahashi, Takuya Takeichi, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 10 ) page： E347 - E348 2023.10

Allergen-specific IgG4 increase in atopic dermatitis with long-term dupilumab use. Reviewed International journal

Mariko Ogawa-Momohara, Yoshinao Muro, Chiaki Murase, Tomoki Taki, Kana Tanahashi, Yuta Yamashita, Haruka Koizumi, Ryo Fukaura, Takuya Takeichi, Masashi Akiyama

The British journal of dermatology Vol. 189 ( 4 ) page： 472 - 474 2023.9

Treatment of Severe Dermatitis, Multiple Allergies, and Metabolic Wasting With Dupilumab. Reviewed International journal

Yuta Koike, Takuya Takeichi, Norito Ishii, Tomoka Waseda, Naoya Murayama, Masashi Akiyama, Hiroyuki Murota

JAMA dermatology Vol. 159 ( 9 ) page： 1009 - 1011 2023.9

Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis. Reviewed International coauthorship International journal

Takuya Takeichi, Takenori Yoshikawa, Muhammad Nasir Iqbal, Muhammad Farooq, Tomoki Taki, Yoshinao Muro, Yutaka Shimomura, Mariko Seishima, Masashi Akiyama

Experimental dermatology Vol. 32 ( 9 ) page： 1557 - 1562 2023.9

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.

DOI： 10.1111/exd.14846

Giant condyloma of Buschke-Löwenstein in a Netherton syndrome patient, successfully treated with cryotherapy and intravenous immunoglobulin. Reviewed International journal

Mirai Sawa, Chiaki Murase, Naoto Yamada, Ryo Fukaura, Nobuyuki Tetsuka, Yoshitaka Sato, Takuya Takeichi, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 9 ) page： E289 - E291 2023.9

Comment on: Successful treatment of rapid progressive interstitial lung disease in a case of anti-Zo antibody positive anti-synthetase syndrome. Reviewed International journal

Haruka Koizumi, Yoshinao Muro, Satoshi Kamiya, Norika Akashi, Satoko Imai, Yuta Yamashita, Mariko Ogawa-Momohara, Takuya Takeichi, Masashi Akiyama

International journal of rheumatic diseases Vol. 26 ( 9 ) page： 1872 - 1873 2023.9

Anti-KIF20B autoantibodies in systemic autoimmune rheumatic diseases: Their high prevalence in systemic lupus erythematosus. Reviewed International coauthorship International journal

Haruka Koizumi, Yoshinao Muro, Yuta Yamashita, Takuya Takeichi, Marvin J Fritzler, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 8 ) page： 990 - 998 2023.8

Language：English Publishing type：Research paper (scientific journal)

The kinesin superfamily protein 20B (KIF20B), also known as M-phase phosphoprotein-1, is a plus-end-directed motor enzyme for cytokinesis. Anti-KIF20B antibodies have been reported in idiopathic ataxia, but no previous studies have examined anti-KIF20B antibodies in systemic autoimmune rheumatic diseases (SARDs). We aimed to establish methods for detecting anti-KIF20B antibodies and to investigate the clinical significance of these antibodies in SARDs. Serum samples from 597 patients with various SARDs and 46 healthy controls (HCs) were included. Fifty-nine samples that had been examined by immunoprecipitation using the recombinant KIF20B protein produced by in vitro transcription/translation were used for establishing the ELISA cutoff with the same recombinant protein for measuring the anti-KIF20B antibodies. The ELISA performed well, showing close agreement with the immunoprecipitation results (Cohen's κ >0.8). The ELISA results for 643 samples showed the prevalence of anti-KIF20B to be higher in the systemic lupus erythematosus (SLE) patients than in the HCs (18/89 vs. 3/46, P = 0.045). Since no SARD other than SLE had higher frequencies of anti-KIF20B antibodies than those of the HCs, we investigated the clinical characteristics of anti-KIF20B antibody-positive cases in SLE. The score on the SLE Disease Activity Index-2000 (SLEDAI-2K) was significantly higher for the anti-KIF20B-positive SLE patients than for the anti-KIF20B-negative SLE patients (P = 0.013). In a multivariate regression analysis of the anti-single-stranded deoxyribonucleic acid, anti-double-stranded deoxyribonucleic acid, and anti-KIF20B antibodies, the presence of anti-KIF20B antibody was significantly associated with high SLEDAI-2K scores (P = 0.003). Anti-KIF20B antibodies were found in ~20% of patients with SLE and were associated with high SLEDAI-2K scores. Much larger cohort and longitudinal studies are needed to confirm the association between anti-KIF20B antibodies and SLE.

DOI： 10.1111/1346-8138.16813

Plucked scalp hair follicle samples are useful RNA sources for mRNA analysis of most genodermatosis-associated genes. Reviewed International journal

So Takeuchi, Takuya Takeichi, Yoshinao Muro, Teppei Shimamura, Masashi Akiyama

Journal of dermatological science Vol. 111 ( 2 ) page： 68 - 70 2023.8

Loss of RhoE function in dermatofibroma promotes disorganized dermal fibroblast extracellular matrix and increased integrin activation. Reviewed International coauthorship International journal

Sofia Endzhievskaya, Chao-Kai Hsu, Hsing-San Yang, Hsin-Yu Huang, Yu-Chen Lin, Yi-Kai Hong, John Y W Lee, Alexandros Onoufriadis, Takuya Takeichi, Julia Yu-Yun Lee, Tanya J Shaw, John A McGrath, Maddy Parsons

The Journal of investigative dermatology Vol. 143 ( 8 ) page： 1487 - 1497.e9 2023.8

Language：English Publishing type：Research paper (scientific journal)

Dermatofibromas are common, benign fibrous skin tumors that can occur at any skin site. In most cases, dermatofibromas are solitary and sporadic, but a few are multiple and familial, and the mechanisms leading to these lesions are currently unclear. Using exome sequencing, we have identified a heterozygous variant in a pedigree with autosomal dominant multiple familial dermatofibromas within RND3 (c.692C>T,p.T231M) that encodes for the small GTPase RhoE, a regulator of the actin cytoskeleton. Expression of T231M-RhoE or RhoE depletion using CRISPR in human dermal fibroblasts increased proliferation, adhesion to extracellular matrix via enhanced β1 integrin activation and more disorganized matrix. The enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was identified as a binding partner for RhoE and formation of this complex was disrupted by T231M-RhoE. PLOD2 promotes collagen crosslinking and activation of β1 integrins, and depleting PLOD2 in T231M-RhoE expressing cells reduced T231M-RhoE-mediated β1 integrin activation and led to increased matrix alignment. Immunohistochemical analysis revealed reduced expression of RhoE but increased expression of PLOD2 in the dermis of dermatofibroma skin samples compared to controls. Our data show loss of RhoE function leads to increased PLOD2 activation, enhancing integrin activation and leading to disorganized extracellular matrix, contributing to dermatofibroma.

DOI： 10.1016/j.jid.2023.01.019