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Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis.

ABSTRACT: Immune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg results were analyzed according to the disease activity score-28 (DAS28). Then sensitivity and specificity were calculated for the indication of the remission status. The number and inhibitory activity of Treg are higher in the clinical remission as compared to the active RA (p value

SUBMITTER: Kanjana K

PROVIDER: S-EPMC7666192 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis.

Kanjana Korawit K Chevaisrakul Parawee P Matangkasombut Ponpan P Paisooksantivatana Karan K Lumjiaktase Putthapoom P

Scientific reports 20201113 1

Immune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg resu ...[more]

PMID: 33188235

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Project description:Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease. Despite the wide use of conventional synthetic, targeted and biologic disease modifying anti-rheumatic drugs (DMARDs) to control its radiological progress, nearly all DMARDs are immunologically non-selective and do not address the underlying immunological mechanisms of RA. Patients with RA often need to take various DMARDs long-term or even lifelong and thus, face increased risks of infection, tumor and other adverse reactions. It is logical to modulate the immune disorders and restore immune balance in patients with RA by restoring immune tolerance. Indeed, approaches based on stem cell transplantation, tolerogenic dendritic cells (tolDCs), and antigen-based tolerogenic vaccination are under active investigation, and some have already transformed from wet bench research to clinical investigation during the last decade. Among them, clinical trials on stem cell therapy, especially mesenchymal stem cells (MSCs) transplantation are most investigated and followed by tolDCs in RA patients. On the other hand, despite active laboratory investigations on the use of RA-specific peptide-/protein-based tolerogenic vaccines for T cell, clinical studies on RA patients are much limited. Overall, the preliminary results of these clinical studies are promising and encouraging, demonstrating their safety and effectiveness in the rebalancing of T cell subsets; particular, the recovery of RA-specific Treg with increasing anti-inflammatory cytokines and reduced proinflammatory cytokines. Future studies should focus on the optimization of transplanted stem cells, the preparation of tolDCs, and tolerogenic vaccines with RA-specific protein or peptide, including their dosage, course, and route of administration with well-coordinated multi-center randomized clinical control researches. With the progress of experimental and clinical studies, generating and restoring RA-specific immune tolerance may bring revolutionary changes to the clinical management of RA in the near future.

Project description:ObjectivePatients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination.MethodsOf the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24-week open-label period. These 253 patients then entered a 48-week, double-blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease-worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run-in period. The primary end point was the proportion of patients in whom SDAI-defined remission was maintained without disease-worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease-worsening, and the proportion of patients in whom SDAI-defined remission was recaptured after initiation of rescue therapy.ResultsBaseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI-defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI-defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease-worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P < 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI-defined remission was recaptured in 70-80% in each treatment group. No new safety signals were reported.ConclusionThe efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI-defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision-making when withdrawal of therapy is being considered to reduce treatment burden in patients with well-controlled RA.

Project description:OBJECTIVE:Most patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score. METHODS:We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score. RESULTS:The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease-modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%-25% probability), and 15% in the moderate remission prediction category (greater than 25% probability). CONCLUSION:We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.

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Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis.

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Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis.

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