T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy.

Sonja Dulic,Gergely Toldi,László Kovács,Balázs Szalay,Zsófia Vásárhelyi,Attila Balog,László Berta,Florentina Sava

doi:10.1155/2017/6894374

Sonja Dulic, Gergely Toldi + Show 6 more

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https://doi.org/10.1155/2017/6894374

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Abstract

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: (1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; (2) in anti-TNF responders as well as in nonresponders, the frequencies of naïve CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; (3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; (4) pending confirmation, a CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA. The ClinicalTrials.gov registration number of our study is NCT03266822.

Highlights

Rheumatoid arthritis (RA) is the most common chronic autoimmune joint disease, which leads to progressive articular destruction without treatment [1]
Fewer interleukin-6 receptor (IL-6R) responders took traditional DMARDs than the anti-tumor necrosis factor-α (TNF)-treated patients, and the proportion of anticitrullinated peptide antibody- (ACPA-) positive patients was lower in the IL-6R blocker-treated group
Our results present a comprehensive overview of the alterations in the composition of the T-cell subset in RA patients on long-term anti-TNF or IL-6R blocker therapy with a focus on changes in the naive/memory subtypes, the most important effector pathways (Th1, Th2, Th17, and that of regulatoryT-cells (Treg)), as well as various activation markers (CD25, CD69, and HLA-DR)

Summary

Introduction

Rheumatoid arthritis (RA) is the most common chronic autoimmune joint disease, which leads to progressive articular destruction without treatment [1]. The abnormal function of CD4+ and CD8+ cells plays a key role in the autoimmune process leading to the development of RA. This is reflected by a number of observations indicating that the proportion of different CD4+ subsets responsible for the harmonized immune response is skewed to a proinflammatory direction. Few studies, including our previous examinations [7], followed T-cell subset prevalence changes, but in most of them, only short-term follow-up was evaluated [8,9,10,11,12,13,14,15]. Data on the effects of IL-6R blocker therapy are especially limited [16,17,18]

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