Find in Library
Search millions of books, articles, and more
Indexed Open Access Databases
Molecular profiling of rheumatoid arthritis patients reveals an association between innate and adaptive cell populations and response to anti-tumor necrosis factor
oleh: 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
Format: | Article |
---|---|
Diterbitkan: | BMC 2019-10-01 |
Deskripsi
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.