Portal de Periódicos da CAPES

Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome

2023; Oxford University Press; Volume: 63; Issue: 8 Linguagem: Inglês

10.1093/rheumatology/kead425

1462-0332

Ayaka Maeda, Naomi Tsuchida, Yuri Uchiyama, Nobuyuki Horita, Satoshi Kobayashi, Mitsumasa Kishimoto, Daisuke Kobayashi, Haruki Matsumoto, Tomoyuki Asano, Kiyoshi Migita, Ayaka Kato, Ichiro Mori, Hiroyuki Morita, Akihiro Matsubara, Yoshiaki Marumo, Yuji Ito, Tomoaki Machiyama, Tsuyoshi Shirai, Tomonori Ishii, Mari Kishibe, Yusuke Yoshida, Shintaro Hirata, Satoshi Akao, Akitsu Higuchi, Ryo Rokutanda, Ken Nagahata, Hiroki Takahashi, Kosuke Katsuo, Toshio Ohtani, Hiroshi Fujiwara, Hiromichi Nagano, Takashi Hosokawa, Takanori Ito, Yoichiro Haji, Hiroyuki Yamaguchi, Noboru Hagino, Toshimasa Shimizu, Tomohiro Koga, Atsushi Kawakami, Goichi Kageyama, Hiroshi Kobayashi, Akiko Aoki, Akinari Mizokami, Yoichi Takeuchi, Rena Motohashi, Hiroyuki Hagiyama, Masaki Itagane, Hiroyuki Teruya, Tomohiro Kato, Yuji Miyoshi, Takayasu Kise, Naoto Yokogawa, Takako Ishida, Naoki Umeda, Shuntaro Isogai, Taio Naniwa, Toru Yamabe, Kaori Uchino, Jo Kanasugi, Akiyoshi Takami, Yasushi Kondo, Kazunori Furuhashi, Koichi Saito, Shigeru Ohno, Daiga Kishimoto, Mari Yamamoto, Yoshiro Fujita, Yuichiro Fujieda, Sachiko Araki, Hiroshi Tsushima, Kyohei Misawa, Akira Katagiri, Takahiro Kobayashi, Kenichi Hashimoto, Takehiro Sone, Yukiko Hidaka, Hiroaki Ida, Ryuta Nishikomori, Hiroshi Doi, Katsumichi Fujimaki, Keiichi Akasaka, Masako Amano, Hidekazu Matsushima, Kaori KASHINO, Hidenori Ohnishi, Yuki Miwa, Noriyuki Takahashi, Kaoru Takase‐Minegishi, Ryusuke Yoshimi, Yohei Kirino, Hideaki Nakajima, Naomichi Matsumoto,

Immunodeficiency and Autoimmune Disorders

Abstract Objectives To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Methods Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median age of onset 69.3 years (interquartile range 62.1–77.6)]. Peptide nucleic acid–clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR or targeted amplicon deep sequencing was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and -negative patients and assessed the diagnostic value of our system using receiver operating characteristics (ROC) curve analysis. Results Forty patients (44.9%) with reported pathogenic UBA1 variants were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering age >50 years, cutaneous lesions, lung involvement, chondritis and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). Conclusion Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.