ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1568431
Patients with peripheral artery disease demonstrate altered expression of soluble and membrane-bound immune checkpoints by peripheral blood immune cells
Provisionally accepted
Rosanne D. Reitsema1
Seta Kurt1,2
Ignacio Rangel1Hans Hjelmqvist1,3Mats Dreifaldt4Allan Sirsjö1
Ashok Kumar Kumawat1*- 1Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
- 2Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- 3Department of Anaesthesia and Intensive Care, Örebro University Hospital, Region Örebro County, Örebro, Sweden
- 4Department of Cardiothoracic Surgery, Örebro University Hospital and University Health Care Research Centre,, Örebro, Sweden
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Studies 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).The 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.Soluble 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. In conclusion: PAD 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.
Keywords: peripheral artery disease, Intermittent Claudication, immune checkpoints, T cells, antigen presenting cells
Received: 29 Jan 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Reitsema, Kurt, Rangel, Hjelmqvist, Dreifaldt, Sirsjö and Kumawat. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ashok Kumar Kumawat, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
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