An interleukin 6 responsive plasma cell signature is associated with disease progression in systemic sclerosis interstitial lung disease

Systemic sclerosis (SSc) interstitial lung disease (ILD) is among the leading causes of SSc-related morbidity and mortality. Tocilizumab (TCZ, anti-IL6RA) has demonstrated a reduced rate of pulmonary function decline in two phase 2/3 trials (faSScinate and focuSSced) in SSc-ILD patients. We performe...

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Veröffentlicht in:iScience 2023-11, Vol.26 (11), p.108133-108133, Article 108133
Hauptverfasser: Jia, Guiquan, Ramalingam, Thirumalai R., Heiden, Jason Vander, Gao, Xia, DePianto, Daryle, Morshead, Katrina B., Modrusan, Zora, Ramamoorthi, Nandhini, Wolters, Paul, Lin, Celia, Khanna, Dinesh, Arron, Joseph R.
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Sprache:eng
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Zusammenfassung:Systemic sclerosis (SSc) interstitial lung disease (ILD) is among the leading causes of SSc-related morbidity and mortality. Tocilizumab (TCZ, anti-IL6RA) has demonstrated a reduced rate of pulmonary function decline in two phase 2/3 trials (faSScinate and focuSSced) in SSc-ILD patients. We performed transcriptome analysis of skin biopsy samples collected in the studies to decipher gene networks that were potentially associated with clinical responses to TCZ treatment. One module correlated with disease progression showed pharmacodynamic changes with TCZ treatment, and was characterized by plasma cell (PC) genes. PC signature gene expression levels were also significantly increased in both fibrotic SSc and IPF lungs compared to controls. scRNAseq analyses confirmed that PC signature genes were co-expressed in CD38 and CD138 expressing PC subsets in SSc lungs. These data provide insights into the potential role of PC in disease progression and mechanisms of action of TCZ in fibrotic interstitial lung diseases. [Display omitted] •Tocilizumab treatment benefits SSc-ILD patients with stabilization of lung function•Skin plasma cell (PC) gene signature is identified responsive to the treatment•The enriched PC signature is associated with lung function of SSc-ILD patients•The enriched PC signature is interrogated and verified in the lung of ILD patients Fibrosis; Biological sciences; Molecular biology; Immunology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.108133