Faculty Profiles - TAKEICHI Takuya

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

Ichthyotic skin phenotype induced by the chronic activation of Toll-like receptor 2, and autoinflammation. Reviewed International journal

Takuya Takeichi, Yoshinao Muro, Masashi Akiyama

The British journal of dermatology Vol. 189 ( 2 ) page： 252 - 252 2023.7

KLK11 ichthyosis: large truncal hyperkeratotic pigmented plaques underscore a distinct autosomal dominant disorder of cornification. Reviewed International coauthorship International journal

Takuya Takeichi, Yasutoshi Ito, John Y W Lee, Chiaki Murase, Yusuke Okuno, Yoshinao Muro, John A McGrath, Masashi Akiyama

The British journal of dermatology Vol. 189 ( 1 ) page： 134 - 136 2023.7

Cutaneous manifestations of microscopic polyangiitis successfully controlled with avacopan alone. Reviewed International journal

Satoshi Kamiya, Haruka Koizumi, Yuika Suzuki, Satoko Imai, Yuta Yamashita, Mariko Ogawa-Momohara, Takuya Takeichi, Yoshinao Muro, Kazushi Yasuda, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 7 ) page： E206 - E207 2023.7

Recent Advances in Clinical Research on Rare Intractable Hereditary Skin Diseases in Japan. Reviewed

Masashi Akiyama, Takuya Takeichi, Shigaku Ikeda, Akira Ishiko, Michiko Kurosawa, Hiroyuki Murota, Yutaka Shimomura, Tamio Suzuki, Katsuto Tamai, Akio Tanaka, Tadashi Terui, Masayuki Amagai

The Keio journal of medicine 2023.6

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

Our Research Group for Rare and Intractable Skin Diseases operates within the Project for Research on Intractable Diseases of the Ministry of Health, Labour, and Welfare of Japan and is conducting research on eight rare intractable skin diseases. Five of these are monogenic disorders (epidermolysis bullosa, congenital ichthyoses, oculocutaneous albinism, pseudoxanthoma elasticum, and hereditary angioedema), and for a sixth [generalized pustular psoriasis (GPP)], genetic predisposing factors are important. This review introduces our activities for raising public awareness of these six intractable hereditary skin diseases and summarizes our recent achievements in clarifying the situation of medical treatments for these diseases in Japan. We note our current progress in elucidating the pathogeneses of these diseases and in developing new treatment methods, and we discuss our progress in establishing clinical practice guidelines. A nationwide survey on epidermolysis bullosa and a clinical survey on congenital ichthyoses are progressing. The Angioedema Activity Score and the Angioedema Quality-of-Life Questionnaire, the latter of which is a quality-of-life evaluation tool, have been established for hereditary angioedema. Registries of patients with oculocutaneous albinism and pseudoxanthoma elasticum have been created, and the registry for the latter has achieved its target of 170 cases. For GPP, the results of our survey on clinical practice were published in 2021. Information regarding all six of these hereditary skin diseases has been disseminated to academic societies, medical professionals, patients, and the general public.

DOI： 10.2302/kjm.2023-0008-IR

Ichthyotic skin lesions of Conradi-Hünermann-Happle syndrome successfully treated with dupilumab. Reviewed International journal

Ryo Fukaura, Takuya Takeichi, Aoi Ebata, Chiaki Murase, Yoshinao Muro, Masashi Akiyama

Journal of the European Academy of Dermatology and Venereology : JEADV Vol. 37 ( 6 ) page： E732 - E734 2023.6

COVID-19 infection- and vaccination-related exacerbation of Darier's disease in a single patient. Reviewed International journal

Ryo Fukaura, Takuya Takeichi, Aoi Ebata, Yoshinao Muro, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 6 ) page： 833 - 836 2023.6

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

Darier's disease (DD) is a rare autosomal dominantly inherited disorder. DD patients usually present with widespread keratotic eruptions with itching in the seborrheic regions that are exacerbated by various factors, including heat, sweat, and physical trauma. The SARS-CoV-2 (COVID-19) pandemic has stirred confusion among the medical community, including dermatologists, as this infection has been implicated in various skin conditions. Only a handful of reports have documented DD associated with COVID-19. Here, we report a 30-year-old male with Darier's disease whose symptoms were exacerbated following both COVID-19 vaccination and COVID-19 infection. The patient had noticed slight eruptions 7 years prior, but was not particularly concerned. After COVID-19 vaccination and infection, he had erythematous maculopapular lesions in large areas of the trunk and extremities. The previously reported pathogenic variant c.2255_2257del (p.(Ile752_Tyr753delinsAsn)) in ATP2A2 was detected in the present patient. Oral etretinate greatly improved his DD manifestations. As far as we know, the present patient is the first genetically confirmed DD case who showed both COVID-19 infection- and vaccination-related DD exacerbations independently. We think that the further accumulation of DD cases exacerbated by COVID-19 infection/vaccination is needed to clarify the mechanisms of DD aggravation.

DOI： 10.1111/1346-8138.16725

Successful combination therapy of bimekizumab and granulocyte monocyte adsorption apheresis for generalized pustular psoriasis complicated with microscopic polyangiitis. Reviewed International journal

Rie Shukuin, Haruka Koizumi, Aoi Ebata, Satoko Imai, Yuta Yamashita, Mariko Ogawa-Momohara, Takuya Takeichi, Yoshinao Muro, Norito Takami, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 6 ) page： E181 - E182 2023.6

The use of certolizumab pegol to successfully treat generalized pustular psoriasis combined with psoriatic uveitis Reviewed International journal

Kazuki Yatsuzuka, Takuya Matsumoto, Yuri Sakane, Ryo Fukaura, Takuya Takeichi, Masashi Akiyama, Masamoto Murakami

The Journal of Dermatology Vol. 50 ( 6 ) page： E175 - E176 2023.6

Current understanding of the phenotypic spectrum of patients with NLRP1 variants. Reviewed International journal

Takuya Takeichi, Masashi Akiyama

The British journal of dermatology Vol. 188 ( 2 ) page： 160 - + 2023.2

Development of pemphigus vegetans and exacerbation of pemphigus foliaceus after secukinumab loading in a patient with complicated generalized pustular psoriasis and pyoderma gangrenosum. Reviewed International journal

Lisa Minai, Takuya Takeichi, Youichi Ogawa, Akiko Honobe-Tabuchi, Takashi Okamoto, Hiroshi Mitsui, Shinji Shimada, Masashi Akiyama, Tatsuyoshi Kawamura

The Journal of dermatology Vol. 50 ( 2 ) page： 245 - 249 2023.2

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

In dermatology, biologics that block signaling pathways of TNF-α, IL-4/IL13, IL-17s, and IL-23 are widely used for the treatment of several inflammatory skin diseases, such as atopic dermatitis and psoriasis. They have shown excellent efficacy with an acceptable safety profile. However, these biologics targeting pathogenic cytokines and their receptors could modulate immunological balance, leading to the development of other inflammatory or autoimmune skin diseases in some cases. In this study, we present a patient who suffered pemphigus vegetans and showed an exacerbation of pemphigus foliaceus after secukinumab loading for the treatment of complicated generalized pustular psoriasis and pyoderma gangrenosum.

DOI： 10.1111/1346-8138.16563