Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity

Objective. The role of T cells in the pathogenesis of systemic lupus erythematosus (SLE) has recently gained attention. Costimulatory molecules are membrane proteins strictly associated with T-cell receptor (TCR), acting by activating or inhibiting T cells and antigen-presenting cells (APC) through...

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Main Authors: Fulvia Ceccarelli, Francesco Natalucci, Alessandra Di Filippo, Giulio Olivieri, Chiara Napoletano, Aurelia Rughetti, Marianna Nuti, Ilaria Grazia Zizzari, Fabrizio Conti
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2023/2344239
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author Fulvia Ceccarelli
Francesco Natalucci
Alessandra Di Filippo
Giulio Olivieri
Chiara Napoletano
Aurelia Rughetti
Marianna Nuti
Ilaria Grazia Zizzari
Fabrizio Conti
author_facet Fulvia Ceccarelli
Francesco Natalucci
Alessandra Di Filippo
Giulio Olivieri
Chiara Napoletano
Aurelia Rughetti
Marianna Nuti
Ilaria Grazia Zizzari
Fabrizio Conti
author_sort Fulvia Ceccarelli
collection DOAJ
description Objective. The role of T cells in the pathogenesis of systemic lupus erythematosus (SLE) has recently gained attention. Costimulatory molecules are membrane proteins strictly associated with T-cell receptor (TCR), acting by activating or inhibiting T cells and antigen-presenting cells (APC) through direct and reverse signaling, thus becoming responsible for the development of effector T cells or regulatory T cells. The primary objective of the present case–control study was to evaluate the cell membrane expression of CD137 on T cells and the serum concentration of CD137 (sCD137) in a SLE cohort. Materials. We enrolled SLE patients and sex/age-matched healthy subjects (HS). Disease activity was assessed by SLEDAI-2K. By application of flow cytometry, we evaluated the expression of CD137 on CD4+ and CD8+ lymphocytes. ELISA test was performed to evaluate serum levels of sCD137. Results. Twenty-one SLE patients (M/F 1/20; median age 48 years (IQR 17); median disease duration 144 months (IQR 204)) were evaluated. SLE patients showed %CD3+CD137+ cells significantly higher compared to HS (median 5.32 (IQR 6.11) versus 3.3 (IQR 1.8), p=0.001). In SLE patients, %CD4+CD137+ cells positively correlated with SLEDAI-2K (p=0.0082, r = 0.58, CI (0.15–0.82); indeed, %CD4+CD137+ cells were significantly lower in SLE patients with a remission status compared to those not reaching this condition (median 1.07 (IQR 0.91) versus 1.58 (IQR 2.42), p=0.013). Accordingly, sCD137 levels were significantly lower in remission status (31.30 pg/mL (IQR 102.2 versus median 122.8 pg/mL (IQR 536); p=0.03) and correlated with %CD4+CD137+ cells (p=0.012, r = 0.60, CI (0.15–0.84)). Conclusion. Our results suggest a possible involvement of CD137-CD137L axis in SLE pathogenesis, as demonstrated by higher expression of CD137 on CD4+ cells in SLE compared with HS. Furthermore, the positive correlation between SLEDAI-2K and membrane CD137 expression on CD4+ cells, as well as soluble CD137, indicates a possible use as biomarkers for disease activity.
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spelling doaj-art-0f9d8e1b7a904e55b7e76b2720b57e4d2025-08-20T03:54:28ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/2344239Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease ActivityFulvia Ceccarelli0Francesco Natalucci1Alessandra Di Filippo2Giulio Olivieri3Chiara Napoletano4Aurelia Rughetti5Marianna Nuti6Ilaria Grazia Zizzari7Fabrizio Conti8Lupus ClinicLupus ClinicLaboratory of Tumor Immunology and Cell TherapyLupus ClinicLaboratory of Tumor Immunology and Cell TherapyLaboratory of Tumor Immunology and Cell TherapyLaboratory of Tumor Immunology and Cell TherapyLaboratory of Tumor Immunology and Cell TherapyLupus ClinicObjective. The role of T cells in the pathogenesis of systemic lupus erythematosus (SLE) has recently gained attention. Costimulatory molecules are membrane proteins strictly associated with T-cell receptor (TCR), acting by activating or inhibiting T cells and antigen-presenting cells (APC) through direct and reverse signaling, thus becoming responsible for the development of effector T cells or regulatory T cells. The primary objective of the present case–control study was to evaluate the cell membrane expression of CD137 on T cells and the serum concentration of CD137 (sCD137) in a SLE cohort. Materials. We enrolled SLE patients and sex/age-matched healthy subjects (HS). Disease activity was assessed by SLEDAI-2K. By application of flow cytometry, we evaluated the expression of CD137 on CD4+ and CD8+ lymphocytes. ELISA test was performed to evaluate serum levels of sCD137. Results. Twenty-one SLE patients (M/F 1/20; median age 48 years (IQR 17); median disease duration 144 months (IQR 204)) were evaluated. SLE patients showed %CD3+CD137+ cells significantly higher compared to HS (median 5.32 (IQR 6.11) versus 3.3 (IQR 1.8), p=0.001). In SLE patients, %CD4+CD137+ cells positively correlated with SLEDAI-2K (p=0.0082, r = 0.58, CI (0.15–0.82); indeed, %CD4+CD137+ cells were significantly lower in SLE patients with a remission status compared to those not reaching this condition (median 1.07 (IQR 0.91) versus 1.58 (IQR 2.42), p=0.013). Accordingly, sCD137 levels were significantly lower in remission status (31.30 pg/mL (IQR 102.2 versus median 122.8 pg/mL (IQR 536); p=0.03) and correlated with %CD4+CD137+ cells (p=0.012, r = 0.60, CI (0.15–0.84)). Conclusion. Our results suggest a possible involvement of CD137-CD137L axis in SLE pathogenesis, as demonstrated by higher expression of CD137 on CD4+ cells in SLE compared with HS. Furthermore, the positive correlation between SLEDAI-2K and membrane CD137 expression on CD4+ cells, as well as soluble CD137, indicates a possible use as biomarkers for disease activity.http://dx.doi.org/10.1155/2023/2344239
spellingShingle Fulvia Ceccarelli
Francesco Natalucci
Alessandra Di Filippo
Giulio Olivieri
Chiara Napoletano
Aurelia Rughetti
Marianna Nuti
Ilaria Grazia Zizzari
Fabrizio Conti
Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity
Journal of Immunology Research
title Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity
title_full Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity
title_fullStr Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity
title_full_unstemmed Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity
title_short Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity
title_sort membrane and soluble cd137 in systemic lupus erythematosus role as biomarkers for disease activity
url http://dx.doi.org/10.1155/2023/2344239
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