Frontiers in Immunology (Sep 2022)

Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience

  • Takayuki Miyamoto,
  • Yoshitaka Honda,
  • Yoshitaka Honda,
  • Yoshitaka Honda,
  • Kazushi Izawa,
  • Nobuo Kanazawa,
  • Saori Kadowaki,
  • Hidenori Ohnishi,
  • Masakazu Fujimoto,
  • Naotomo Kambe,
  • Naoya Kase,
  • Takeshi Shiba,
  • Yasuo Nakagishi,
  • Shuji Akizuki,
  • Kosaku Murakami,
  • Masahiro Bamba,
  • Yutaka Nishida,
  • Ayano Inui,
  • Tomoo Fujisawa,
  • Daisuke Nishida,
  • Naomi Iwata,
  • Yoshikazu Otsubo,
  • Shingo Ishimori,
  • Momoko Nishikori,
  • Kiminobu Tanizawa,
  • Tomoyuki Nakamura,
  • Takeshi Ueda,
  • Yoko Ohwada,
  • Yu Tsuyusaki,
  • Masaki Shimizu,
  • Takasuke Ebato,
  • Kousho Iwao,
  • Akiharu Kubo,
  • Toshinao Kawai,
  • Tadashi Matsubayashi,
  • Tatsuhiko Miyazaki,
  • Tomohiro Kanayama,
  • Masahiko Nishitani-Isa,
  • Hiroshi Nihira,
  • Junya Abe,
  • Junya Abe,
  • Takayuki Tanaka,
  • Takayuki Tanaka,
  • Eitaro Hiejima,
  • Satoshi Okada,
  • Osamu Ohara,
  • Megumu K. Saito,
  • Junko Takita,
  • Ryuta Nishikomori,
  • Takahiro Yasumi

DOI
https://doi.org/10.3389/fimmu.2022.905960
Journal volume & issue
Vol. 13

Abstract

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PurposeUpregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature.MethodsThe type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature.ResultsA total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling.ConclusionsHalf of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.

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