Allergy, Asthma and Immunology

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October 5, 2023

Multifaceted analysis of cross-tissue transcriptomes reveals phenotype–endotype associations in atopic dermatitis

  • Article
  • Open Access

  • Aiko Sekita, 
  • Hiroshi Kawasaki, 
  • Ayano Fukushima-Nomura, 
  • Kiyoshi Yashiro, 
  • Keiji Tanese, 
  • Susumu Toshima, 
  • Koichi Ashizaki, 
  • Tomohiro Miyai, 
  • Junshi Yazaki, 
  • Atsuo Kobayashi, 
  • Shinichi Namba, 
  • Tatsuhiko Naito, 
  • Qingbo S. Wang, 
  • Eiryo Kawakami, 
  • Jun Seita, 
  • Osamu Ohara, 
  • Kazuhiro Sakurada, 
  • Yukinori Okada, 
  • Masayuki Amagai & 
  • Haruhiko Koseki

Nature Communications volume 14, Article number: 6133 (2023) 

  • details

Abstract

Atopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures.
We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases.

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Publicado por ivancev@gmail.com en 8:25 AM
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ORCID Juan C. Ivancevich

ORCID iD iconhttps://orcid.org/0000-0001-8713-6258

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