Dataset Information

Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4+ Treg Cells in Patients with Rheumatoid Arthritis.

ABSTRACT: BACKGROUND/AIMS:Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4+ cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge. METHODS:Comprehensive analyses were carried out by Flow cytometry. Expression of Helios, CD226, T cell immunoreceptor with Ig and ITIM domains clinical samples and healthy controls. RESULTS:We have systemically examined three potential markers, Helios, CD226 and TIGIT, that are possibly related to Treg identification, and found that Helios expression on CD4+Foxp3+cells was decreased and negatively correlated with the disease activity of RA patients, while CD226 and TIGIT both showed elevated expression levels in CD4+Foxp3+cells in RA patients and they were not associated with disease activity of RA patients. CONCLUSION:Taken together, our findings indicate that CD4+CD25hiCD127low/-Foxp3+Helios+ may represent the real Treg cell population in patients with RA.

SUBMITTER: Yang M

PROVIDER: S-EPMC6943339 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4<sup>+</sup> Treg Cells in Patients with Rheumatoid Arthritis.

Yang Mengru M Liu Yan Y Mo Biyao B Xue Youqiu Y Ye Congxiu C Jiang Yutong Y Bi Xuan X Liu Meng M Wu Yunting Y Wang Julie J Olsen Nancy N Pan Yunfeng Y Zheng Song Guo SG

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20190101 5

<h4>Background/aims</h4>Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4<sup>+</sup> cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge.<h4>Methods</h4>Comprehensive analyses were carried ...[more]

PMID: 30990587

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Project description:BackgroundPrognostic biomarkers of treatment response to distinct biologic disease-modifying anti-rheumatic drugs (b-DMARDs) are still lacking within the management of rheumatoid arthritis (RA).MethodsThirty-four b-DMARDs naive RA patients, divided by disease duration into early (cohort 1) and long standing (cohort 2), received CTLA4-Ig. At study entry, and every 3 months for 1 year, each patient underwent peripheral blood (PB)-derived CD4pos cell subpopulation assessment by flow cytometry, STAT3 and STAT5 expression by RT-PCR and IL-6, IL-12p70, TGFβ, and IL-10 serum levels by ELISA. The DAS and CDAI remission was assessed at 6 and 12 months.ResultsDAS- and CDAI-defined remission within 12 months was achieved by 16 (47.1%) and 8 (23.5%) RA patients, respectively. Considering the whole RA cohort, CTLA4-Ig induced a significant decrease of IL-6 serum levels from baseline to 6 and 12 months, as well as of PB CD4posCD25posFoxP3pos cells at 6 and 12 months, and of CD4posIL17pos cells after 12 months. PB CD4pos cells of RA patients showed higher STAT3 and STAT5 expression than healthy controls, which remained unchanged within 12 months of treatment. At study entry, RA patients achieving DAS remission had significantly lower IL-6 serum levels than RA patients not achieving this outcome. In particular, having baseline IL-6 serum levels ≤ 8.4 pg/ml, significantly identified naïve to b-DMARDs RA patients more likely to achieve DAS-remission under CTLA4-Ig at 6 months (66.7%) compared to RA patients with baseline IL-6 serum levels > 8.4 pg/ml [15.4%, OR (95%Cis) 11.00 (1.75-55.82)]. Moreover, having CD4posCD25posFoxP3pos cells rate ≥ 6.0% significantly identifies naïve to b-DMARDs early RA patients more likely to achieve DAS remission at 6 months (83.3%) compared to RA patients with baseline CD4posCD25posFoxP3pos cells < 6.0% [16.7%, OR (95% Cis) 25.00 (1.00-336.81)].ConclusionsBaseline IL-6 serum levels and peripheral blood-derived CD4pos subpopulations are putative novel prognostic biomarkers of CTLA4-Ig response in RA patients.

Dataset Information

Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4+ Treg Cells in Patients with Rheumatoid Arthritis.

Publications

Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4<sup>+</sup> Treg Cells in Patients with Rheumatoid Arthritis.

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