2. Academic Validation
  3. Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF

Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF

  • Arthritis Res Ther. 2020 May 7;22(1):106. doi: 10.1186/s13075-020-02198-9.
Yun-Jeong Song 1,  In Ah Choi 2,  Françoise Meylan 1,  M Kristen Demoruelle 3,  Taylor Farley 1,  Arianne C Richard 1,  Eric Hawley 1,  John Botson 1,  Yoo Jin Hong 2,  Eun Young Lee 2,  Sabina R Mian 4,  Bartlett C Hamilton 5,  Geoffrey M Thiele 5,  Ted R Mikuls 5,  Naveen Gara 6,  Chris D Ward 7,  Sarah Lamberth 8,  Kevin D Deane 3,  Theo Heller 6,  Michael M Ward 9,  David M Lee 10 11,  Thi-Sau Migone 7,  William Stohl 4,  James R O'Dell 5,  Jill M Norris 12,  V Michael Holers 3,  Peter Gregersen 13,  Yeong-Wook Song 2,  Richard M Siegel 14
Affiliations

Affiliations

  • 1 Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, MD, USA.
  • 2 Division of Rheumatology, Department of Internal Medicine, MMBS, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
  • 3 Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, 80207, USA.
  • 4 Division of Rheumatology, Department of Medicine, Los Angeles County University of Southern California Medical Center and University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  • 5 Rheumatology Division, Department of Medicine, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
  • 6 Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
  • 7 Human Genome Sciences, Rockville, MD, USA.
  • 8 Immunology Biomarkers group, Pharmaceutical Companies of J&J, LLC, Spring House, PA, USA.
  • 9 Clinical Trials and Outcomes Branch, NIAMS, NIH, Bethesda, MD, USA.
  • 10 Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • 11 Present address: Janssen Research and Development, Spring House, PA, USA.
  • 12 Colorado School of Public Health, Aurora, CO, USA.
  • 13 Center for Genomics & Human Genetics, The Feinstein Institute for Medical Research, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, USA.
  • 14 Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, MD, USA. richardmsiegel@gmail.com.
PMID: 32381123 DOI: 10.1186/s13075-020-02198-9
Abstract

Background: The tumor necrosis factor (TNF) superfamily cytokine TNF-like protein 1A (TL1A) and its receptor DR3 are essential for diverse animal models of autoimmune disease and may be pathogenic in rheumatoid arthritis (RA). However, the relationship of TL1A to disease duration, activity, and response to anti-TNF and Other therapies in RA is not clear.

Methods: We measured soluble TL1A in synovial fluid (SF), serum, or plasma from RA first-degree relatives (FDRs) and in early RA and established disease. We measured the effects of anti-TNF and methotrexate (MTX) therapy on circulating TL1A from multiple independent RA treatment trials. We also determined the ability of a blocking anti-TL1A antibody to inhibit clinical disease and articular bone destruction in the murine collagen-induced arthritis (CIA) model of human RA.

Results: Soluble TL1A was specifically elevated in the blood and SF of patients with RA compared to patients with Other Diseases and was elevated early in disease and in at-risk anti-cyclic citrullinated peptide (CCP) (+) first-degree relatives (FDRs). Therapeutic TNF inhibition reduced serum TL1A in both responders and non-responders, whereas TL1A declined following MTX treatment only in responders. In murine CIA, TL1A blockade was clinically efficacious and reduced bone erosions.

Conclusions: TL1A is specifically elevated in RA from early in the disease course and in at-risk FDRs. The decline in TL1A after TNF blockade suggests that TL1A levels may be a useful biomarker for TNF activity in RA. These results support the further investigation of the relationship between TL1A and TNF and TL1A blockade as a potential therapeutic strategy in RA.

Keywords

Collagen-induced arthritis; Cytokines; Rheumatoid arthritis; TNFSF15; Tumor necrosis factor-like cytokine 1A.

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