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

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.

The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing Spondylitis

“…There are many similarities in these results and our previous observations in RA patients [16]. The present measurements confirm our previous conclusions that the major mechanism of action of anti-TNF therapy is not the restoration of the activated immune system – observed in active disease – to a state similar to healthy individuals, in terms of the T-cell subset distribution.…”

“…The expansion of Th17 and Th1 cells has been described by other authors too [23, 24], and we observed a similar phenomenon in RA too [16]. A potential explanation has been presented by Notley et al [25], who have shown that anti-TNF treatment of mice in the collagen-induced arthritis model led to the upregulation of the p40 subunit of the IL-12/23 receptor and a resulting increase in both Th17 and Th1 cell frequencies.…”

“…Furthermore, low Th17 cell frequencies predicted a good European League against Rheumatism response to anticytokine (including anti-TNF) therapies, whereas high CD24 hi CD27+ B reg prevalences were predictors to response to abatacept in RA [22]. We have revealed that low CD4CD69 cell frequency at the initiation of anti-TNF therapy was a good predictor of treatment response to anti-TNF treatment in RA [16]. However, data are much scarcer in relation to AS, in which an increase in Th17 cell frequencies has also been revealed during anti-TNF treatment [12], but opposing results have also been obtained by others [11].…”

“…The applied medication is often missing from the cohort descriptions. Importantly, only 1 study analyzed patients with relatively long-standing anti-TNF treatment (6 months) [11], whereas 2 further investigations, including our previous work, followed the T-cell repertoire only for a short time (6 weeks) [12, 14], although we have recently demonstrated in our study of rheumatoid arthritis (RA) patients that there are profound differences in the T-cell subset distribution after short-term or long-term follow-up [16]. …”

“…The aim of our comprehensive study is to give a well-described pathogenic overview of various T-cell subsets in AS before and during short- and long-term anti-TNF therapy, as we did in our previous work in this field in RA [16]. We intended to examine whether there is a difference between anti-TNF responder and anti-TNF nonresponder AS patients as well, and we compare the long-term anti-TNF-treated AS patients (more than 6 months) with our previous data on therapy-naïve and short-term (6 weeks) anti-TNF-treated AS patients too.…”