Faculty Profiles - TAKEICHI Takuya

Mutations in SAM syndrome and palmoplantar keratoderma patients suggest genotype/phenotype correlations in DSG1 mutations Reviewed

Case of harlequin ichthyosis in preterm infant with a compound heterozygous ABCA12 missense mutation. Reviewed International journal

Moeka Miyazaki, Natsuki Ohkawa, Kazuki Miyabayashi, Hiromichi Shoji, Takuya Takeichi, Masato Kantake, Masashi Akiyama, Toshiaki Shimizu

The Journal of dermatology Vol. 49 ( 4 ) page： E137 - E139 2022.4

S. Takeuchi, T. Takeichi, Y. Koike, H. Takama, K. Tanahashi, Y. Okuno, N. Ishii, Y. Muro, T. Ogi, Y. Suga, M. Akiyama

Journal of the European Academy of Dermatology and Venereology Vol. 36 ( 3 ) page： E215 - E218 2022.3

Anti-Zo antibodies in Japanese myositis patients detected by a newly developed ELISA Reviewed

Muro Y., Hashimoto T., Izumi S., Ogawa-Momohara M., Takeichi T., Yamashita H., Yasuoka H., Akiyama M.

Clinical and experimental rheumatology Vol. 40 ( 2 ) page： 219 - 223 2022.2

Differential pathomechanisms of desmoglein-1 transmembrane domain mutations in skin disease. Reviewed International journal

Stephanie E Zimmer, Takuya Takeichi, Daniel E Conway, Akiharu Kubo, Yasushi Suga, Masashi Akiyama, Andrew P Kowalczyk

The Journal of investigative dermatology Vol. 142 ( 2 ) page： 323 - + 2022.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Dominant and recessive mutations in the desmosomal cadherin, desmoglein-1 (DSG1), cause the skin diseases palmoplantar keratoderma (PPK) and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, respectively. Here, we compare two dominant missense mutations in the DSG1 transmembrane domain (TMD), G557R and G562R, causing PPK (DSG1PPK-TMD) and SAM syndrome (DSG1SAM-TMD), respectively, to determine the differing pathomechanisms of these mutants. Expressing the DSG1TMD mutants in a DSG-null background, we use cellular and biochemical assays to reveal differences in the mechanistic behavior of each mutant. Super resolution microscopy and functional assays showed a failure by both mutants to assemble desmosomes due to reduced membrane trafficking and lipid raft targeting. DSG1SAM-TMD maintained normal expression levels and turnover relative to DSG1WT, but DSG1PPK-TMD lacked stability, leading to increased turnover through lysosomal and proteasomal pathways and reduced expression levels. These results differentiate the underlying pathomechanisms of these disorders, suggesting that DSG1SAM-TMD acts dominant negatively while DSG1PPK-TMD is a loss-of-function mutation causing the milder PPK disease phenotype. These mutants portray the importance of the DSG TMD in desmosome function and suggest that a greater understanding of the desmosomal cadherin TMDs will further our understanding of the role that desmosomes play in epidermal pathophysiology.

DOI： 10.1016/j.jid.2021.07.154

Long-term risk of cancer development among anti-Th/To antibody-positive systemic sclerosis patients: comment on the article by Mecoli et al. Reviewed International journal

Yuta Yamashita, Yasuhiko Yamano, Yoshinao Muro, Haruka Koizumi, Takuya Takeichi, Yasuhiro Kondoh, Masashi Akiyama

Arthritis & rheumatology (Hoboken, N.J.) Vol. 74 ( 2 ) page： 368 - 369 2022.2

Language：English Publisher：WILEY

We read the report by Mecoli et al on the relationship between cancer and anti-Th/To antibodies (AThAs) in patients with systemic sclerosis (SSc) (1). It is interesting that the presence of AThAs was reported to confer a protective effect against cancer development in those patients. However, cancer development in AThA-positive patients was significantly suppressed only within the first 3 years after SSc onset, and there was no significant difference in the number of deceased between the AThA-positive and AThA-negative patients.

DOI： 10.1002/art.41945

Anti-Zo antibodies in Japanese myositis patients detected by a newly developed ELISA Reviewed

Muro Y., Hashimoto T., Izumi S., Ogawa-Momohara M., Takeichi T., Yamashita H., Yasuoka H., Akiyama M.

CLINICAL AND EXPERIMENTAL RHEUMATOLOGY Vol. 40 ( 2 ) page： 219 - 223 2022.2

Autoinflammatory Keratinization Disease With Hepatitis and Autism Reveals Roles for JAK1 Kinase Hyperactivity in Autoinflammation. Reviewed International coauthorship International journal

Takuya Takeichi, John Y W Lee, Yusuke Okuno, Yuki Miyasaka, Yuya Murase, Takenori Yoshikawa, Kana Tanahashi, Emi Nishida, Tatsuya Okamoto, Komei Ito, Yoshinao Muro, Kazumitsu Sugiura, Tamio Ohno, John A McGrath, Masashi Akiyama

Frontiers in immunology Vol. 12 page： 737747 - 737747 2022.1

Language：English Publishing type：Research paper (scientific journal) Publisher：FRONTIERS MEDIA SA

Heterozygous mutations in JAK1 which result in JAK-STAT hyperactivity have been implicated in an autosomal dominant disorder that features multi-organ immune dysregulation. This study identifies another previously unreported heterozygous missense JAK1 mutation, H596D, in an individual with a unique autoinflammatory keratinization disease associated with early-onset liver dysfunction and autism. Using CRISPR-Cas9 gene targeting, we generated mice with an identical Jak1 knock-in missense mutation (Jak1 H595D/+;I596I/+;Y597Y/+ mice) that recapitulated key aspects of the human phenotype. RNA sequencing of samples isolated from the Jak1 H595D/+;I596I/+;Y597Y/+ mice revealed the upregulation of genes associated with the hyperactivation of tyrosine kinases and NF-κB signaling. Interestingly, there was a strong correlation between genes downregulated in Jak1 H595D/+;I596I/+;Y597Y/+ mice and those downregulated in the brain of model mice with 22q11.2 deletion syndrome that showed cognitive and behavioral deficits, such as autism spectrum disorders. Our findings expand the phenotypic spectrum of JAK1-associated disease and underscore how JAK1 dysfunction contributes to this autoinflammatory disorder.

DOI： 10.3389/fimmu.2021.737747

FOXA1 mutations in extramammary Paget's disease

Takeichi T.

Nishinihon Journal of Dermatology Vol. 84 ( 1 ) page： 9 - 12 2022

A Case of Family with Vörner-type Palmoplantar Keratoses Confirmed by Genetic Analysis

Matsumoto K., Kaneko S., Takeuchi S., Takeichi T., Akiyama M.

Nishinihon Journal of Dermatology Vol. 84 ( 5 ) page： 418 - 421 2022

Pitfalls in establishing mouse model of female infertility by immunization with human centromere protein. Reviewed International journal

Yoshinao Muro, Yuta Yamashita, Haruka Koizumi, Takuya Takeichi, Masashi Akiyama

Immunology letters Vol. 239 page： 20 - 22 2021.11

Extensive multiple organ involvement in VEXAS syndrome. Reviewed International journal

Noriyuki Takahashi, Takuya Takeichi, Tetsuya Nishida, Yasuhiro Takahashi, Juichi Sato, Masahiro Yamamura, Tomoo Ogi, Masashi Akiyama

Arthritis & rheumatology (Hoboken, N.J.) Vol. 73 ( 10 ) page： 1896 - 1897 2021.10

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

A 55-year-old Japanese man was diagnosed with VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, which is a newly documented adult-onset autoinflammatory disease caused by somatic UBA1 mutations [1], after four years of symptoms. He had suffered from recurrent fever after the onset of systemic arthralgia, scleritis, periorbital/orbital inflammation, optic perineuritis (A, B, T1-weighted contrast-enhanced magnetic resonance imaging in C and D, arrow in D), and myelodysplastic syndrome.

DOI： 10.1002/art.41775

Successful dupilumab treatment for ichthyotic and atopic features of Netherton syndrome Reviewed

Murase C., Takeichi T., Taki T., Yoshikawa T., Suzuki A., Ogi T., Suga Y., Akiyama M.

JOURNAL OF INVESTIGATIVE DERMATOLOGY Vol. 141 ( 10 ) page： S177 - S177 2021.10

A case of generalised pustular psoriasis with bullous pemphigoid showing spongiform pustule of Kogoj with eosinophils. Reviewed International journal

Hiroyoshi Nozaki, Shin Iinuma, Shigetsuna Komatsu, Yoshio Hashimoto, Hikaru Shibaki, Takuya Takeichi, Norito Ishii, Masashi Akiyama, Masaru Honma, Akemi Ishida-Yamamoto

European journal of dermatology : EJD Vol. 31 ( 5 ) page： 660 - 662 2021.9

Case of annular pustular psoriasis/circinate erythematous psoriasis induced by hydroxychloroquine in a patient with systemic lupus erythematosus: Possible association with CARD-14 mutation. Reviewed International journal

Hirotaka Midorikawa, Yukiko Kiniwa, Akane Minagawa, Kana Osawa, Takushi Shirai, Tasuku Sano, Kenta Nakamura, Atsuko Ashida, Ken-Ichi Ueno, Takuya Takeichi, Masashi Akiyama, Ryuhei Okuyama

The Journal of dermatology Vol. 48 ( 9 ) page： E440 - E442 2021.9

Intravenous allogeneic multilineage-differentiating stress-enduring cells in adults with dystrophic epidermolysis bullosa: a phase 1/2 open-label study. Reviewed International journal

Y Fujita, T Nohara, S Takashima, K Natsuga, M Adachi, K Yoshida, S Shinkuma, T Takeichi, H Nakamura, O Wada, M Akiyama, A Ishiko, H Shimizu

Journal of the European Academy of Dermatology and Venereology : JEADV Vol. 35 ( 8 ) page： E528 - E531 2021.8

Cutaneous malignant melanoma in an elderly patient with intermediate junctional epidermolysis bullosa. Reviewed International journal

Yuta Yamashita, Tomoki Taki, Takuya Takeichi, Mao Okumura, Shoichiro Mori, Yasutoshi Ito, Tomoo Ogi, Motohito Yamada, Masashi Akiyama

The Journal of dermatology Vol. 48 ( 8 ) page： E384 - E385 2021.8

Immune recognition of lysyl-tRNA synthetase and isoleucyl-tRNA synthetase by anti-OJ antibody-positive sera. Reviewed International journal

Yoshinao Muro, Yasuhiko Yamano, Ken Yoshida, Yohsuke Oto, Kimiko Nakajima, Teruyuki Mitsuma, Shiori Kikuchi, Akihiro Matsumae, Mariko Ogawa-Momohara, Takuya Takeichi, Yasuhiro Kondoh, Masao Katayama, Yasuyuki Todoroki, Yoshiya Tanaka, Minoru Satoh, Masashi Akiyama

Journal of autoimmunity Vol. 122 page： 102680 - 102680 2021.8

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

OBJECTIVE: Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are useful for identifying a clinical subset of patients with idiopathic inflammatory myopathies (IIMs). Anti-OJ antibodies, which recognize multi-enzyme synthetase complexes including isoleucyl-tRNA synthetase (IARS) and lysyl-tRNA synthetase (KARS), are among the anti-ARS antibodies. Although testing antibodies to other ARSs have been used clinically, no validated immunoassays for detecting anti-OJ antibodies are available. We aimed to establish an anti-OJ ELISA. METHODS: Serum samples were collected from 279 patients with IIMs and 22 patients with idiopathic interstitial pneumonia. Sixty-four of the samples that had been confirmed to be negative for anti-OJ by standard immunoprecipitation were used as the negative control, and 12 anti-OJ-positive reference sera were used as the positive control. Antibodies to IARS and KARS were assayed by ELISA using biotinylated recombinant proteins generated by in vitro transcription/translation. RESULTS: The anti-OJ-positive sera strongly reacted with the KARS and IARS recombinant proteins in ELISA. Although all 12 reference sera were positive in the anti-KARS ELISA, 4 of the 64 anti-OJ-negative sera were also weakly positive. The sensitivity and the specificity were 100% and 93.8%, respectively. Since our anti-KARS ELISA performed well, showing a high agreement with the results for immunoprecipitation (Cohen's κ > 0.8), the remaining 237 samples were also tested. Thirteen anti-KARS-positive sera were newly found by ELISA, all of which were anti-OJ positive by immunoprecipitation. CONCLUSION: Immunoassays for detecting anti-OJ antibodies using KARS and IARS recombinant proteins were developed. Our ELISAs performed well, with very high agreement of the results by immunoprecipitation and can be applied to the first reliable, easy-to-use measurement assays for anti-OJ antibodies.

DOI： 10.1016/j.jaut.2021.102680