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May 20, 2026American Journal of Respiratory and Critical Care Medicine

C70-21 Sex-Specific Transcriptional Networks Associated With Elexacaftor-Tezacaftor-Ivacaftor (ETI) Therapies

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Authors

SBS BluesteinCKC KnightHYH Yin

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Overview

Randomized trial identifies sex-specific transcriptional networks in cystic fibrosis after ETI therapy, suggesting new personalized treatment strategies.

Key Points

  • This study aims to identify transcriptional networks sensitive to Elexacaftor-Tezacaftor-Ivacaftor therapies in cystic fibrosis and their sex-specific impacts.
  • Compared immune transcriptional networks in CF patients (5 males, 7 females) before and after ETI therapy.
  • Collected and analyzed sputum samples via scRNAseq for gene expression profiling.
  • Utilized a standardized Connectome pipeline with R package Seurat 4.3.1.
  • In females, the IL1RN to IL1R2 edgeweight increased from 0.50 to 0.70 after ETI therapy, while in males it decreased from 0.44 to 0.28.
  • An increase in the IL15 to IL2RA edgeweight was noted in females, whereas it remained constant in males.
  • Observed a reduction in outgoing monocyte signaling and fewer edgeweights between monocytes and other cell types in treated females.

Cite This Study

Bluestein et al. (2026) studied this question.

synapsesocial.com/papers/6a0d50cdf03e14405aa9cea0https://doi.org/10.1093/ajrccm/aamag162.2178
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1A76-22 Sex Differences in Clinical Outcomes Among Adults With Cystic Fibrosis After Initiation of Elexacaftor/Tezacaftor/Ivacaftor: Analysis From a Multi-center Prospective Study2026
  2. 2B33-11 Single-Cell RNA-Sequencing Reveals Deactivation of Inflammatory Responses in Cystic Fibrosis Classical Monocytes Following Elexacaftor/Tezacaftor/Ivacaftor Therapy2026
  3. 3B107-17 High Exacerbators in Cystic Fibrosis Have Sex-Specific Monocyte Transcriptomes2026
  4. 4The effect of highly effective modulator therapy on systemic inflammation in cystic fibrosis2024 · 3 citations
  5. 5CFTR modulator therapy reshapes airway inflammation in cystic fibrosis: Insights from proteomics and machine learning2026 · 1 citations