Comparative Transcriptional Profiling of Key Macrophage and Fibroblast Subpopulations in Rheumatoid Arthritis–Associated Lung Disease - Summary - MDSpire

Differential Gene Expression Analysis of Major Macrophage and Fibroblast Subtypes in Lung Disease Related to Rheumatoid Arthritis

  • By

  • Tracy Tabib

  • Ogechukwu Ezenwa

  • Joshua Sciurba

  • Eleanor B. Valenzi

  • John Sembrat

  • Brittany Cody

  • Jishnu Das

  • Robert Lafyatis

  • Dana P. Ascherman

  • July 8, 2026

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Objective:

To characterize transcriptomic profiles of RA-ILD lung tissue using single-cell RNA sequencing and understand the role of macrophage and fibroblast subpopulations in RA-ILD and its relationship to IPF.

Approach:
  • Sample Processing: Fresh lung tissue samples from RA-ILD patients and controls were processed using poly(A) capture–based scRNA-seq, while archived specimens were analyzed using Flex scRNA-seq, allowing for comparative analysis of different sample types.
Key Findings:
  • RA-ILD is associated with significant morbidity and mortality, rivaling cardiovascular disease.
  • Up to 30% of RA patients exhibit subclinical ILD without significant symptoms.
  • Machine learning tools identified protein mediators that distinguish RA-ILD from RA without ILD.
  • A composite biomarker profile linked to IPF was elevated in some individuals with subclinical RA-ILD.
  • Single-cell RNA sequencing revealed shared macrophage-fibroblast interactions promoting pulmonary fibrosis.
Interpretation:

The study provides insights into the immunopathogenesis of RA-ILD, focusing on macrophage and fibroblast interactions in disease progression.

Limitations:
  • Potential restricted translocation of protein mediators from lung tissue to systemic circulation.
  • Confounding factors from proinflammatory/profibrotic mediators originating from other tissues in RA.
Conclusion:

The findings enhance understanding of the molecular mechanisms underlying RA-ILD and its similarities with IPF.

Original Source(s)

Comparative Transcriptional Profiling of Key Macrophage and Fibroblast Subpopulations in Rheumatoid Arthritis–Associated Lung Disease

  • by Tracy Tabib, Ogechukwu Ezenwa, Joshua Sciurba, Eleanor B. Valenzi, John Sembrat, Brittany Cody, Jishnu Das, Robert Lafyatis, Dana P. Ascherman

  • July 8, 2026

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