Peripheral Biomarker Signatures in Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Details

• Alternative Title:
  Arthritis & Rheumatology (Hoboken, N.J.), 2025, v. 77, no. 8: Peripheral Biomarker Signatures in Rheumatoid Arthritis-Associated Interstitial Lung Disease.
• Journal Article:
  Arthritis & Rheumatology (Hoboken, N.J.)
• Personal Author:
  Wheeler, Austin M. ; Baker, Joshua F. ; Riley, Thomas R. ; Johnson, Tate M. ; Yang, Yangyuna ; Roul, Punyasha ; Wysham, Katherine D. ; Cannon, Grant W. ; Kunkel, Gary ; Kerr, Gail ; Ascherman, Dana P. ; Monach, Paul ; Reimold, Andreas ; Matson, Scott ; Poole, Jill A. ; Duryee, Michael J. ; Thiele, Geoffrey M. ; Mikuls, Ted R. ; England, Bryant R.
• Description:
  Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant cause of morbidity and mortality among patients with RA, yet effective risk stratification for RA-ILD is lacking. We sought to characterize unique peripheral blood biomarker signatures in RA that could improve RA-ILD discrimination beyond clinical and genetic risk factors.
  
  We performed a cross-sectional study of participants in the Veterans Affairs Rheumatoid Arthritis Registry. ILD was validated through systematic record review. Autoantibodies (n = 14), proinflammatory cytokines/chemokines (n = 36), adipokines (n = 3), alarmins (n = 3), and matrix metalloproteinases (n = 9) were measured from banked serum or plasma. MUC5B rs35705950 genotyping was obtained via microarray. Principal component (PC) analysis was performed to derive unique biomarker signatures. Logistic regression was used to compare models predicting RA-ILD presence using combinations of clinical, peripheral biomarker, and genetic variables.
  
  Among 2,001 participants with RA (88.7% male, mean age 63.7 years), 121 (6.4%) had RA-ILD. A total of 15 PCs were identified, with 8 significantly associated with RA-ILD after adjusting for clinical factors. These eight included biomarker themes of innate and allergic responses, autoantibodies (anti-cyclic citrullinated peptide, rheumatoid factor, anti-malondialdehyde-acetaldehyde adduct), adipokines, alarmins, tissue remodeling, and neutrophil chemotaxis. Models with PCs (area under the receiver operating characteristic curve AUC 0.739) and PCs with MUC5B (AUC 0.751) outperformed clinical risk factors alone (AUC 0.630; P < 0.001).
  
  Peripheral biomarker signatures are associated with RA-ILD and improve RA-ILD identification beyond clinical risk factors. In addition to demonstrating the potential for peripheral biomarkers to aid RA-ILD risk stratification, these findings suggest diverse pathways are involved in RA-ILD pathogenesis.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Male
  • Arthritis, Rheumatoid
  • Female
  • Biomarkers
  • Middle Aged
  • Lung Diseases, Interstitial
  • Cross-Sectional Studies
  • Aged
  • Autoantibodies
  More +
• Keywords:
  • rheumatoid arthritis
  • interstitial lung disease
  • peripheral biomarkers
  • principal component analysis
• Source:
  Arthritis & Rheumatology (Hoboken, N.J.), 2025, v. 77, no. 8
• DOI:
  https://doi.org/10.1002/art.43149
• ISSN:
  2326-5191 ; 2326-5205
• Pubmed ID:
  40033001
• Pubmed Central ID:
  PMC12311258
• Document Type:
  Text
• Funding:
  5T32GM075766-17/NH/NIH HHSUnited States/ ; I01 CX001703/CX/CSRD VAUnited States/ ; I01 RX003644/RX/RRD VAUnited States/ ; R01OH012045/OH/NIOSH CDC HHSUnited States/ ; 1U54GM115458/NH/NIH HHSUnited States/ ; I01 BX003635/BX/BLRD VAUnited States/ ; IK2 CX002351/CX/CSRD VAUnited States/ ; T32 GM075766/GM/NIGMS NIH HHSUnited States/ ; RX003644/U.S. Department of Veterans Affairs/ ; CX001703/U.S. Department of Veterans Affairs/ ; PR200793/U.S. Department of Defense/ ; U54 GM115458/GM/NIGMS NIH HHSUnited States/ ; Rheumatology Research Foundation/ ; IK2 CX002203/CX/CSRD VAUnited States/ ; R01 OH012045/OH/NIOSH CDC HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  971-980 (19 pdf pages)
• Volume:
  77
• Issue:
  8
• Download URL:
  https://stacks.cdc.gov/view/cdc/261633/cdc_261633_DS1.pdf
• File Type:
  [PDF - 570.67 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0ec7a85cbebef39dcf8a7738eb77ecda4f77c6149aabaa787bb260c02d9bcf16ffd6409720aa96492ad5730242a4baae781d1819170544943f1abee848f6f27a