Unique Transcriptomic Profile of Peripheral Blood Monocytes in Rheumatoid Arthritis-associated Interstitial Lung Disease.

Details

• Alternative Title:
  Rheumatology (Oxford, England), 2025, v. 64: Unique Transcriptomic Profile of Peripheral Blood Monocytes in Rheumatoid Arthritis-associated Interstitial Lung Disease.
• Journal Article:
  Rheumatology (Oxford, England)
• Personal Author:
  Poole, Jill A. ; Schwab, Aaron ; Thiele, Geoffrey M. ; England, Bryant R. ; Nelson, Amy J. ; Gleason, Angela ; Duryee, Michael J. ; Bailey, Kristina L. ; Romberger, Debra J. ; Hershberger, Daniel ; Van de Graaff, Joel ; May, Sara M. ; Walenz, Rhonda ; Kramer, Bridget ; Mikuls, Ted R.
• Description:
  Though interstitial lung disease (ILD) contributes to excess morbidity and mortality in rheumatoid arthritis (RA), RA-ILD pathogenesis remains incompletely defined. As intermediate, non-classical and suppressed CD14+ monocytes are expanded in RA-ILD, this study sought to characterize gene expression profiles of circulating monocytes in RA-ILD.
  
  Peripheral blood mononuclear cells were collected from patients with RA without lung disease (n = 5), RA-ILD (n = 5), idiopathic pulmonary fibrosis (IPF; n = 5), and controls without lung and autoimmune disease (n = 4). RNA was extracted from CD14+ isolated monocytes and subjected to transcriptional analysis of 1365 genes. Gene enrichment and pathway analyses were performed.
  
  Unsupervised clustering grouped patients with RA-ILD together with IPF for myeloid innate genes. For fibrosis genes, patients with RA-ILD clustered independent of comparator groups. There were 103, 66 and 64 upregulated and 66, 14 and 25 downregulated genes for RA-ILD, RA, and IPF, vs controls, respectively. For RA-ILD, there was increased expression of genes involved in regulating inflammation and fibrosis (SOCS3, CECAM1, LTB4R2, CLEC7A, IRF7, PHYKPL, GBP5, RAPGEF), epigenetic modification (KDM5D, KMT2D, OGT) and macrophage activation. Top canonical pathways included macrophage differentiation-activation, IL-12, neuroinflammatory, glucocorticoid receptor and IL-27 signalling.
  
  Circulating monocytes in RA-ILD patients demonstrate unique gene expression profiles, with innate immune gene features more aligned with IPF as opposed to RA in the absence of clinical lung disease, and with fibrosis gene expression that was distinct from RA and IPF. These studies are important for understanding disease pathogenesis and may provide information for future therapeutic targets in RA-ILD.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Arthritis, Rheumatoid
  • Monocytes
  • Lung Diseases, Interstitial
  • Female
  • Male
  • Middle Aged
  • Transcriptome
  • Aged
  • Idiopathic Pulmonary Fibrosis
  More +
• Keywords:
  • interstitial lung disease
  • rheumatoid arthritis
  • monocyte
  • circulating
  • blood
  • gene
  • pathway
• Source:
  Rheumatology (Oxford, England), 2025, v. 64
• DOI:
  https://doi.org/10.1093/rheumatology/keae572
• ISSN:
  1462-0324 ; 1462-0332
• Pubmed ID:
  39412518
• Pubmed Central ID:
  PMC12498283
• Document Type:
  Text
• Funding:
  P20 GM103427/GM/NIGMS NIH HHSUnited States/ ; P30 CA036727/CA/NCI NIH HHSUnited States/ ; U54 GM115458/GM/NIGMS NIH HHSUnited States/ ; I01 BX004660/BX/BLRD VAUnited States/ ; IK2 CX002203/CX/CSRD VAUnited States/ ; R01 OH012045/OH/NIOSH CDC HHSUnited States/ ; I01 BX003635/BX/BLRD VAUnited States/ ; I01 BX006049/BX/BLRD VAUnited States/ ; PR200793/Department of Defence/ ; R01OH012045/National Institute of Occupational Safety and Health/ ; I01 BX004660/BX/BLRD VAUnited States/ ; I01 BX003635/BX/BLRD VAUnited States/ ; 2U54GM115458/National Institute of Health/ ; Rheumatology Research Foundation/
• Genre:
  Journal Article
• Pages in Document:
  SI37-SI46 (20 pdf pages)
• Volume:
  64
• Download URL:
  https://stacks.cdc.gov/view/cdc/262136/cdc_262136_DS1.pdf
• File Type:
  [PDF - 1.83 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:01f1acbddd7c7e0794a3c572f91a990f7125e8b1bd95de5dc465443fb64bbe9a9b3ecf04abe7db131b14e3fb3941adce84bf511f0dbcdbf199df4fb251181b68