Faculty Profiles - TAKEICHI Takuya

Whole-exome sequencing reveals a retinitis pigmentosa-causative PRPH2 variant as a secondary finding in a patient with pseudoxanthoma elasticum. International journal

Akira Miyazaki, Takuya Takeichi, Kana Tanahashi, Tomoki Taki, Yosuke Taki, Yoshinao Muro, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 2 ) page： e85 - e86 2023.2

A case of juvenile amyopathic dermatomyositis with anti-transcription intermediary factor 1-α antibody showing negative anti-TIF1-γ ELISA results: Comment on "Case of pembrolizumab-induced dermatomyositis with anti-transcription intermediary factor 1-γ antibody". Reviewed International journal

Haruka Koizumi, Yoshinao Muro, Satoko Imai, Yuta Yamashita, Mariko Ogawa-Momohara, Takuya Takeichi, Megumi Murakami, Teruyuki Mitsuma, Masashi Akiyama

The Journal of dermatology Vol. 50 ( 1 ) page： E39 - E40 2023.1

Novel homozygous missense mutation c.1654G>T in the ALOX12B gene causing congenital ichthyosiform erythroderma. Reviewed International journal

Kotoe Mae, Yoshio Kawakami, Ai Kajita, Takuya Takeichi, Tatsuhiro Noda, Yoji Hirai, Masashi Akiyama, Shin Morizane

The Journal of dermatology Vol. 50 ( 1 ) page： E37 - E38 2023.1

Comment on: Disease evolution in a long-term follow-up of 104 undifferentiated connective tissue disease patients. Reviewed International journal

Yuta Yamashita, Yoshinao Muro, Haruka Koizumi, Mariko Ogawa-Momohara, Takuya Takeichi, Masashi Akiyama

Clinical and experimental rheumatology Vol. 41 ( 1 ) page： 195 - 196 2023.1

Comment on: Disease evolution in a long-term follow-up of 104 undifferentiated connective tissue disease patients Reviewed International journal

Yamashita Y., Muro Y., Koizumi H., Ogawa-Momohara M., Takeichi T., Akiyama M.

CLINICAL AND EXPERIMENTAL RHEUMATOLOGY Vol. 41 ( 1 ) page： 195 - 196 2023.1

Occurrence of cholangiocarcinoma, three years after negative seroconversion of anti-TIF1γ antibody, in a dermatomyositis patient. Reviewed International journal

Ken Horisaki, Yoshinao Muro, Mariko Ogawa-Momohara, Yuta Yamashita, Haruka Koizumi, Takuya Takeichi, Masashi Akiyama

European journal of dermatology : EJD Vol. 33 ( 1 ) page： 48 - 49 2023.1

Appropriate immunoassay systems are needed to evaluate various anticentromere antibodies as biomarkers for disease progression in systemic sclerosis. Reviewed International journal

Yoshinao Muro, Yuta Yamashita, Haruka Koizumi, Mariko Ogawa-Momohara, Takuya Takeichi, Masashi Akiyama

Journal of immunological methods Vol. 512 page： 113400 - 113400 2023.1

Two novel anti-aminoacyl tRNA synthetase antibodies: Autoantibodies against cysteinyl-tRNA synthetase and valyl-tRNA synthetase. Reviewed International journal

Yoshinao Muro, Yuta Yamashita, Haruka Koizumi, Mariko Ogawa-Momohara, Takuya Takeichi, Teruyuki Mitsuma, Masashi Akiyama

Autoimmunity reviews Vol. 21 ( 12 ) page： 103204 - 103204 2022.12

Language：English

Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are useful for identifying a clinical subset of patients with inflammatory myopathies. Since the myositis of anti-ARS-positive patients is characterized by a unique set of non-myopathic manifestations, including interstitial lung disease, mechanic's hands, and arthralgia, the patients are classified as having anti-synthetase syndrome. Autoantibodies have been identified to eight kinds of ARSs. Of the other 12 ARSs, eight are components of the "OJ" multi-synthetase complex. Autoantibodies to the four remaining ARSs (CysARS, ValARS, SerARS, and TrpARS) have not been reported to be present in patients with inflammatory myopathies. In this study, we first screened samples from more than 300 Japanese patients majorly consisting of those with dermatomyositis (DM) by our established in-house ELISA to find autoantibodies against the four ARSs described above. Since sera from two DM patients specifically reacted to CysARS or ValARS, we determined their reactivities by immunoprecipitation (IP) with the corresponding recombinant proteins and IP-Western blotting with cellular extract. One patient had several features found in anti-synthetase syndrome, but the other did not. The clinical differences among the various anti-ARS antibodies should be explored in a future work.

DOI： 10.1016/j.autrev.2022.103204

Ceramide analysis in combination with genetic testing may provide a precise diagnosis for self-healing collodion babies. International journal

Takuya Takeichi, Yusuke Ohno, Kana Tanahashi, Yasutoshi Ito, Ken Shiraishi, Ryo Utsunomiya, Satoshi Yoshida, Kenta Ikeda, Hayato Nomura, Shin Morizane, Koji Sayama, Tomoo Ogi, Yoshinao Muro, Akio Kihara, Masashi Akiyama

Journal of lipid research Vol. 63 ( 12 ) page： 100308 - 100308 2022.12

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

Self-healing collodion baby (SHCB), also called "self-improving collodion baby", is a rare mild variant of autosomal recessive congenital ichthyosis and is defined as a collodion baby who shows the nearly complete resolution of scaling within the first 3 months to 1 year of life. However, during the neonatal period, it is not easy to distinguish SHCB from other inflammatory forms of autosomal recessive congenital ichthyosis, such as congenital ichthyosiform erythroderma. Here, we report a case study of two Japanese SHCB patients with compound heterozygous mutations, c.235G>T (p.(Glu79*))/ c.1189C>T (p.(Arg397Cys)) and c.1295A>G (p.(Tyr432Cys))/ c.1138delG (p.(Asp380Thrfs*3)), in CYP4F22, which encodes cytochrome P450, family 4, subfamily F, polypeptide 22 (CYP4F22). Immunohistochemically, inflammation with the strong expression of IL-17C, IL-36γ, and TNF-α was seen in the skin at birth. CYP4F22 is an ultra-long-chain fatty acid (FA) ω-hydroxylase responsible for ω-O-acylceramide (acylceramide) production. Among the epidermal ceramides, acylceramide is a key lipid in maintaining the epidermal permeability barrier function. We found that the levels of ceramides with ω-hydroxy FAs including acylceramides and the levels of protein-bound ceramides were much lower in stratum corneum samples obtained by tape stripping from SHCB patients than in those from their unaffected parents and individuals without SHCB. Additionally, our cell-based enzyme assay revealed that two mutants, p.(Glu79*) and p.(Arg397Cys), had no enzyme activity. Our findings suggest that genetic testing coupled with non-invasive ceramide analyses using tape-stripped stratum corneum samples might be useful for the early and precise diagnosis of congenital ichthyoses, including SHCB.

DOI： 10.1016/j.jlr.2022.100308

Clinical characteristics of systemic sclerosis patients with anti-NOR90 antibodies

Yamashita, Y; Muro, Y; Koizumi, H; Ogawa-Momohara, M; Takeichi, T; Akiyama, M

JOURNAL OF INVESTIGATIVE DERMATOLOGY Vol. 142 ( 12 ) page： S204 - S204 2022.12

Ceramide profiling of stratum corneum in Sjögren-Larsson syndrome. Reviewed International journal

Ayami Arai, Takuya Takeichi, Hiroyuki Wakamoto, Takayuki Sassa, Yasutoshi Ito, Yuya Murase, Tomoo Ogi, Masashi Akiyama, Akio Kihara

Journal of dermatological science Vol. 107 ( 3 ) page： 114 - 122 2022.9

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

BACKGROUND: Sjögren-Larsson syndrome (SLS) is a neurocutaneous disorder whose causative gene is the fatty aldehyde dehydrogenase ALDH3A2 and of which ichthyosis is the major skin symptom. The stratum corneum contains a variety of ceramides, among which ω-O-acylceramides (acylceramides) and protein-bound ceramides are essential for skin permeability barrier formation. OBJECTIVES: To determine the ceramide classes/species responsible for SLS pathogenesis and the enzymes that are impaired in SLS. METHODS: Genomic DNA was collected from peripheral blood samples from an SLS patient and her parents, and whole-genome sequencing and Sanger sequencing were performed. Lipids were extracted from stratum corneum samples from the SLS patient and healthy volunteers and subjected to ceramide profiling via liquid chromatography coupled with tandem mass spectrometry. RESULTS: A duplication (c.55_130dup) and a missense mutation (p.Lys447Glu) were found in the patient's ALDH3A2 gene. The patient had reduced levels of all acylceramide classes, with total acylceramide levels at 25 % of healthy controls. Reductions were also observed for several nonacylated ceramides: ceramides with phytosphingosine or 6-hydroxysphingosine in the long-chain base moiety were reduced to 24 % and 41 % of control levels, respectively, and ceramides with an α-hydroxy fatty acid as the fatty acid moiety were reduced to 29 %. The fatty acid moiety was shortened in many nonacylated ceramide classes. CONCLUSION: These results suggest that reduced acylceramide levels are a primary cause of the ichthyosis symptoms of SLS, but reductions in other ceramide classes may also be involved.

DOI： 10.1016/j.jdermsci.2022.08.003

Comment on: Favourable complete remission of anti-OJ antibody-positive myositis after lung cancer resection. Reviewed International journal

Yoshinao Muro, Kazuki Nishida, Yuta Yamashita, Haruka Koizumi, Takuya Takeichi, Minoru Satoh, Masashi Akiyama

Rheumatology (Oxford, England) Vol. 61 ( 8 ) page： E232 - E234 2022.8

Extremely mild dominant dystrophic epidermolysis bullosa: Genotype information from whole-exome sequencing of salivary gDNA predicts disease severity. Reviewed International journal

Akira Miyazaki, Takuya Takeichi, So Takeuchi, Tomoki Taki, Yoshinao Muro, Masashi Akiyama

The Journal of dermatology Vol. 49 ( 8 ) page： E276 - E277 2022.8

Eosinophilic granulomatosis with polyangiitis complicated with idiopathic thrombocytopenic purpura and sclerosing cholangitis showing eosinophilic infiltration. Reviewed International journal

Yuta Yamashita, Takuya Takeichi, Yoji Ishizu, Nobuaki Suzuki, Takashi Tsuboi, Kentaro Matsuura, Haruka Koizumi, Yoshinao Muro, Masashi Akiyama

The Journal of dermatology Vol. 49 ( 8 ) page： E270 - E271 2022.8

Darier disease successfully treated with a topical agent containing vitamin A (retinyl palmitate), vitamin E, and urea. Reviewed International journal

Akira Miyazaki, Tomoki Taki, Takuya Takeichi, Michihiro Kono, Hiroaki Yagi, Masashi Akiyama

The Journal of dermatology Vol. 49 ( 8 ) page： 779 - 782 2022.8

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

Darier disease (DD), also called keratosis follicularis, is an autosomal dominant hereditary keratinization disorder that manifests as keratotic papules with plaques in seborrheic areas. There are no validated curative treatments for DD, with the majority of cases treated symptomatically. We report the efficacy of a topical over-the-counter agent which contains retinyl palmitate, vitamin E, and urea for a patient with DD. A 13-year-old girl had brown papules on her scalp, neck, shoulders, and axillae since entering elementary school. A skin biopsy revealed hyperkeratosis, suprabasal acantholysis, and dyskeratosis manifested as corps ronds and grains in the epidermis. Sanger sequencing found the previously reported heterozygous mutation c.1484C>T in ATP2A2. The application of an over-the-counter topical agent containing retinyl palmitate 2750 μg/g (5000 IU/g), tocopheryl acetate 20 mg/g, urea 200 mg/g, and monoammonium glycyrrhizinate 5 mg/g twice daily for 2 months improved the papules without serious adverse events. Oral or topical aromatic vitamin A analogs (retinoids) are often used to treat DD. However, several adverse events are associated with retinoid treatment, and many patients only undergo their intermittent use or discontinue the treatments. Retinyl palmitate is more stable and has a lower irritative profile than other retinoic acids. When applied topically, however, retinyl palmitate cannot penetrate the skin as well as retinol can. Some reports have noted that vitamin E increases the biological availability of vitamin A and that urea helps mechanical percutaneous drug delivery. Our case suggests that retinyl palmitate has a sufficient therapeutic effect when combined with vitamin E and urea. In conclusion, we propose that topical agents containing retinyl palmitate, vitamin E, and urea might have a satisfactory effect on the skin lesions of DD patients, without the serious risks of adverse events.

DOI： 10.1111/1346-8138.16395

Case of ichthyosis with confetti caused by KRT10 mutation, complicated with multiple malignant melanomas. Reviewed International journal

Yasutoshi Ito, Takuya Takeichi, Koichi Nakagawa, Kana Tanahashi, Yoshinao Muro, Tomoo Ogi, Masashi Akiyama

The Journal of dermatology Vol. 49 ( 7 ) page： E228 - E229 2022.7

Deep Phenotyping of Superficial Epidermolytic Ichthyosis due to a Recurrent Mutation in KRT2. Reviewed International journal

Yuika Suzuki, Takuya Takeichi, Kana Tanahashi, Yoshinao Muro, Yasushi Suga, Tomoo Ogi, Masashi Akiyama

International journal of molecular sciences Vol. 23 ( 14 ) 2022.7

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

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient's age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.

DOI： 10.3390/ijms23147791

UVB-Induced Skin Autoinflammation Due to Nlrp1b Mutation and Its Inhibition by Anti-IL-1β Antibody. Reviewed International journal

Yuya Murase, Takuya Takeichi, Jun Koseki, Yuki Miyasaka, Yoshinao Muro, Tamio Ohno, Teppei Shimamura, Masashi Akiyama

Frontiers in immunology Vol. 13 page： 876390 - 876390 2022.6

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

NLRP1 (NACHT and leucine-rich repeat-containing protein family, pyrin domain-containing protein 1) is an innate immune sensor that is involved in the formation of inflammasome complexes. NLRP1 hyperactivity has been reported to cause inherited autoinflammatory diseases including familial keratosis lichenoides chronica and NLRP1-associated autoinflammation with arthritis and dyskeratosis. We generated Nlrp1b (the mouse homologue of human NLRP1) gain-of-function knock-in (Nlrp1b KI) mice with UVB irradiation-induced autoinflammatory skin lesions. We demonstrated that UVB irradiation induces IL-1β upregulation and IL-1β-dependent inflammation via caspase-1 activation in these Nlrp1b KI mice. RNA sequencing revealed the upregulation of inflammasome pathway-related genes, keratinocyte stress marker genes, and keratinocyte differentiation marker genes in the Nlrp1b KI mice after UVB irradiation. The skin inflammation and hyperkeratosis from UVB irradiation in the Nlrp1b KI mice were inhibited by both intraperitoneal and subcutaneous administration of anti-IL-1β antibodies before UVB irradiation. UVB irradiation and the IL-1β pathway are important in the pathogenesis of NLRP1-associated autoinflammatory skin lesions.

DOI： 10.3389/fimmu.2022.876390