Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints
IntroductionStudies suggest that immune checkpoints play a role in accelerating the formation of atherosclerosis. We aimed to assess the expression of soluble and membrane-bound immune checkpoints in patients with peripheral artery disease (PAD).MethodsThe levels of 14 soluble immune checkpoints wer...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568431/full |
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| author | Rosanne D. Reitsema Seta Kurt Seta Kurt Ignacio Rangel Hans Hjelmqvist Hans Hjelmqvist Mats Dreifaldt Allan Sirsjö Ashok Kumar Kumawat |
| author_facet | Rosanne D. Reitsema Seta Kurt Seta Kurt Ignacio Rangel Hans Hjelmqvist Hans Hjelmqvist Mats Dreifaldt Allan Sirsjö Ashok Kumar Kumawat |
| author_sort | Rosanne D. Reitsema |
| collection | DOAJ |
| description | IntroductionStudies suggest that immune checkpoints play a role in accelerating the formation of atherosclerosis. We aimed to assess the expression of soluble and membrane-bound immune checkpoints in patients with peripheral artery disease (PAD).MethodsThe levels of 14 soluble immune checkpoints were assessed in blood plasma of PAD patients (n= 37) and healthy controls (HCs, n=39) by Multiplex protein assay. The surface expression of immune checkpoints on peripheral blood immune cells was determined by flow cytometry. Cytokine production capacity was measured by flow cytometry in TIM-3+ T cells to determine immune exhaustion.ResultsSoluble levels of PD-L2 were decreased in female PAD patients, whereas soluble levels of TIM-3 showed a trend towards an increased concentration in female PAD patients. PD-L2+ frequencies were higher within all monocyte subsets in PAD patients. CD4+ T cells from PAD patients had increased frequencies of TIM-3+ cells, showing little overlap with other immune exhaustion markers. TIM-3+ CD4+ T cells from both PAD patients and HCs, had a low capacity to produce pro-inflammatory cytokines, but a higher capacity to produce IL-10 compared to TIM-3- CD4+ T cells.ConclusionPAD patients show differences in the expression of membrane-bound and soluble immune checkpoints. Some of these differences might be caused by prolonged immune activation, although immune exhaustion markers did not always overlap. |
| format | Article |
| id | doaj-art-04ca25ab4a6843f8bb79a119c171680f |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-04ca25ab4a6843f8bb79a119c171680f2025-08-20T03:51:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15684311568431Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpointsRosanne D. Reitsema0Seta Kurt1Seta Kurt2Ignacio Rangel3Hans Hjelmqvist4Hans Hjelmqvist5Mats Dreifaldt6Allan Sirsjö7Ashok Kumar Kumawat8Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, SwedenFaculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, SwedenDepartment of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, SwedenFaculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, SwedenFaculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, SwedenDepartment of Anaesthesia and Intensive Care, Örebro University Hospital, Region Örebro County, Örebro, SwedenDepartment of Cardiothoracic Surgery, Örebro University Hospital and University Health Care Research Centre, Örebro, SwedenFaculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, SwedenFaculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, SwedenIntroductionStudies suggest that immune checkpoints play a role in accelerating the formation of atherosclerosis. We aimed to assess the expression of soluble and membrane-bound immune checkpoints in patients with peripheral artery disease (PAD).MethodsThe levels of 14 soluble immune checkpoints were assessed in blood plasma of PAD patients (n= 37) and healthy controls (HCs, n=39) by Multiplex protein assay. The surface expression of immune checkpoints on peripheral blood immune cells was determined by flow cytometry. Cytokine production capacity was measured by flow cytometry in TIM-3+ T cells to determine immune exhaustion.ResultsSoluble levels of PD-L2 were decreased in female PAD patients, whereas soluble levels of TIM-3 showed a trend towards an increased concentration in female PAD patients. PD-L2+ frequencies were higher within all monocyte subsets in PAD patients. CD4+ T cells from PAD patients had increased frequencies of TIM-3+ cells, showing little overlap with other immune exhaustion markers. TIM-3+ CD4+ T cells from both PAD patients and HCs, had a low capacity to produce pro-inflammatory cytokines, but a higher capacity to produce IL-10 compared to TIM-3- CD4+ T cells.ConclusionPAD patients show differences in the expression of membrane-bound and soluble immune checkpoints. Some of these differences might be caused by prolonged immune activation, although immune exhaustion markers did not always overlap.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568431/fullperipheral artery diseaseintermittent claudicationimmune checkpointsT cellsantigen presenting cells |
| spellingShingle | Rosanne D. Reitsema Seta Kurt Seta Kurt Ignacio Rangel Hans Hjelmqvist Hans Hjelmqvist Mats Dreifaldt Allan Sirsjö Ashok Kumar Kumawat Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints Frontiers in Immunology peripheral artery disease intermittent claudication immune checkpoints T cells antigen presenting cells |
| title | Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints |
| title_full | Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints |
| title_fullStr | Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints |
| title_full_unstemmed | Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints |
| title_short | Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints |
| title_sort | patients with peripheral artery disease demonstrate altered expression of soluble and membrane bound immune checkpoints |
| topic | peripheral artery disease intermittent claudication immune checkpoints T cells antigen presenting cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568431/full |
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