Resolution of Th/Tc17‐driven inflammation during anti‐TNFα treatment of rheumatoid arthritis reveals a unique immune biomarker profiling pattern

Resolution of Th/Tc17‐driven inflammation during anti‐TNFα treatment of rheumatoid arthritis reveals a unique immune biomarker profiling pattern

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....

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Bibliographic Details
Published in:Scandinavian journal of immunology Vol. 95; no. 1; pp. e13116 - n/a
Main Authors: Bjarnadóttir, Una, Einarsdóttir, Helga K., Stefánsdóttir, Elínborg, Helgason, Einar Axel, Jónasdóttir, Dagrún, Gudmundsson, Sveinn, Gudbjornsson, Bjorn, Ludviksson, Björn R.
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-01-2022
Subjects:
Adult
Aged
Aged, 80 and over
anti‐TNFα treatment
Arthritis, Rheumatoid - chemically induced
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - immunology
biomarker model
Biomarkers
Biomarkers - blood
Cytokines
Cytokines - blood
Female
Helper cells
Humans
Iceland
Immune response
Inflammation
Inflammation - immunology
Innate immunity
Lymphocyte Count
Lymphocytes T
Male
Middle Aged
Patients
Remission
Remission (Medicine)
Rheumatoid arthritis
T cells
T-Lymphocytes, Regulatory - immunology
Th1 Cells - immunology
Th17 Cells - immunology
Treatment Outcome
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor necrosis factor-α
γ-Interferon
Iceland
cytokines
T cells
anti‐TNFα treatment
rheumatoid arthritis
biomarker model
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Summary: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.
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ISSN:0300-9475
1365-3083
DOI:10.1111/sji.13116