Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis
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Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis. / Hsieh, Ting Yu; Lui, Shan Wen; Lu, Jeng Wei; Chen, Yen Chen; Lin, Ting Chun; Jheng, Wun Long; Ho, Yi Jung; Liu, Feng Cheng.
I: In Vivo, Bind 37, Nr. 5, 2023, s. 2018-2027.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis
AU - Hsieh, Ting Yu
AU - Lui, Shan Wen
AU - Lu, Jeng Wei
AU - Chen, Yen Chen
AU - Lin, Ting Chun
AU - Jheng, Wun Long
AU - Ho, Yi Jung
AU - Liu, Feng Cheng
N1 - Publisher Copyright: Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
PY - 2023
Y1 - 2023
N2 - BACKGROUND/AIM: Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. MATERIALS AND METHODS: We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. RESULTS: Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). CONCLUSION: Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.
AB - BACKGROUND/AIM: Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. MATERIALS AND METHODS: We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. RESULTS: Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). CONCLUSION: Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.
KW - autoimmune
KW - Breg
KW - csDMARD
KW - immunophenotyping
KW - rheumatoid arthritis
KW - Tr1
KW - Treg
U2 - 10.21873/invivo.13299
DO - 10.21873/invivo.13299
M3 - Journal article
C2 - 37652509
AN - SCOPUS:85169397928
VL - 37
SP - 2018
EP - 2027
JO - In Vivo
JF - In Vivo
SN - 0258-851X
IS - 5
ER -
ID: 366762704