Resolution of Th/Tc17-driven inflammation during anti-TNF alpha treatment of rheumatoid arthritis reveals a unique immune biomarker profiling pattern

Una Bjarnadóttir, Helga K. Einarsdóttir, Elínborg Stefánsdóttir, Einar Axel Helgason, Dagrún Jónasdóttir, Sveinn Guðmundsson, Björn Guðbjörnsson, Björn Rúnar Lúðvíksson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Rheumatoid arthritis (RA) is a chronic multisystem disease with a complex immunopathology. Its inflammatory state is dominated by pro-inflammatory cytokines such as TNFα and activated Th1/Th17. Only proportion of patients achieve clinical remission despite potent biologics targeting these pathways. This study investigated the resolution of inflammation in RA patients (naïve for biologics) receiving TNFα inhibitors (TNFi) and evaluated the biological mechanisms behind treatment response and assessed them using clinical scoring systems. The majority showed a good clinical response after six months (6M) and a significant drop in DAS28-CRP (P ≤.002), CDAI (P ≤.0001) and RheumXpert (P ≤.0001). Before treatment, the patients demonstrated a chronic innate and adaptive inflammatory state. The improved clinical condition was reflected with a decrease in Th17/Tc17 (P ≤.05) and an increase in Tregs after 6M (P ≤.05). Using a logistic regression model on serum data, IL-6, IL-18, IL-21, IL-22, IFNγ and TNFα were identified as the main contributing biomarkers in the chronic inflammatory state of RA. A specific test score (STS) was defined and converted to a single cytokine composite test score (CCTS), which showed the disease outcome on a scale 0-100, providing sensitivity and specificity of ≥90%. Thus, the immunological complexity in RA is driven by a complex interplay of pro-inflammatory cytokines and effector T-cell response dominated by Th17/Tc17. In addition, the resolution of inflammation could be linked to a partially Treg-driven homeostatic innate immune response. Therefore, a more complex therapeutic approach against the above markers might be of value to obtain full clinical remission in the future.

Original languageEnglish
Article numbere13116
JournalScandinavian Journal of Immunology
Volume95
Issue number1
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

Funding Information:
The authors would especially like to thank Ubaldo Benitez Hernandez for his kind contributions and assistance regarding the Stata software and the determination of the logistical regression model. Special thanks to the nurses of the Department of Rheumatology Landspitali for collecting blood samples from our RA patients and administering the TNFi treatment. We would also like to thank all the blood donors and the staff at the Icelandic Blood Bank for their participation and contribution to the study.

Publisher Copyright:
© 2021 The Scandinavian Foundation for Immunology.

Other keywords

  • anti-TNFα treatment
  • biomarker model
  • cytokines
  • rheumatoid arthritis
  • T cells
  • Immunology
  • General Medicine
  • Arthritis, Rheumatoid

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