Arthritis Research & Therapy (Oct 2019)

Molecular profiling of rheumatoid arthritis patients reveals an association between innate and adaptive cell populations and response to anti-tumor necrosis factor

  • Victor Farutin,
  • Thomas Prod’homme,
  • Kevin McConnell,
  • Nathaniel Washburn,
  • Patrick Halvey,
  • Carol J. Etzel,
  • Jamey Guess,
  • Jay Duffner,
  • Kristen Getchell,
  • Robin Meccariello,
  • Bryan Gutierrez,
  • Christopher Honan,
  • Ganlin Zhao,
  • Nicholas A. Cilfone,
  • Nur Sibel Gunay,
  • Jan L. Hillson,
  • David S. DeLuca,
  • Katherine C. Saunders,
  • Dimitrios A. Pappas,
  • Jeffrey D. Greenberg,
  • Joel M. Kremer,
  • Anthony M. Manning,
  • Leona E. Ling,
  • Ishan Capila

DOI
https://doi.org/10.1186/s13075-019-1999-3
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 14

Abstract

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Abstract Background The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA). Methods Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database. Results A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p < 0.01) between the two cohorts. A baseline, response signature of increased innate cell types in responders compared to increased adaptive cell types in non-responders was identified in both cohorts. This result was further assessed by applying the cell type-specific analysis to five other publicly available RA datasets. Evaluation of the neutrophil-to-lymphocyte ratio at baseline in the remaining patients (n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03–1.41, p = 0.02]). Conclusion Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.

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