Available online 3 April 2024, 114027

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The frequencies of LAG-3+PD-1+, LAG-3+ and PD-1+ cells were significantly increased in CKD patients.

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The frequencies of LAG-3+PD-1+, LAG-3+ and PD-1+ expression on CD8 and CD4 significantly increased in CKD patients with MACE.

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CD8+LAG-3+ cells, CD4+LAG-3+PD-1+ cells, CD4+PD-1+ cells, IL-1β and IL-6 were identified as risk factors for the occurrence of MACE in patients with CKD.

AbstractObjective

Our objective was to study the frequency of circulating LAG-3+ and PD-1+ T cells in chronic kidney disease (CKD) patients and their correlation with cytokines and patient prognosis.

Methods

A total of 83 patients with CKD between June 2020 and June 2022 were enrolled. We measured serum levels of IL-6, CRP, IL-1β, and TNF-α by ELISA. The frequency of PD-1+ and LAG-3+ T cells was measured using flow cytometry. All patients were followed up for 1 year, and the occurrence of any of the following conditions during the follow-up period was considered as major adverse cardiac events (MACE) indicating poor prognosis.

Results

The frequencies of LAG-3+PD-1+, LAG-3+ and PD-1+ cells were significantly increased in CKD group compared to healthy volunteers. Additionally, CKD patients had remarkably enhanced levels of cytokines. Compared to the non-MACE group, MACE group had significantly higher frequencies of LAG-3PD-1, LAG-3 and PD-1 expression on CD8 and CD4. Positive correlations were observed between IL-1β, IL-6 and frequencies of PD-1+LAG-3+. CD4+LAG-3+PD-1+ frequency displayed the highest diagnostic value for CKD patients with MACE. Moreover, CD8+LAG-3+, CD4+LAG-3+PD-1+, CD4+PD-1+, IL-1β and IL-6 were identified as risk factors for the occurrence of MACE in patients with CKD.

Conclusion

In summary, the present research showed that the frequencies of LAG-3+ and PD-1+ T cells were remarkably enhanced in CKD patients. These findings offer novel insights and potential therapeutic targets for the management of CKD.

Section snippetsBackground

Chronic kidney disease (CKD) is a progressive condition [1], and it has been reported that approximately 37 million people in the United States, or about 15% of adults, are affected by CKD [2]. CKD represents a global health burden, with more than half of end-stage renal disease (ESRD) patients succumbing to cardiovascular ailments [[3], [4], [5]]. Early screening of CKD patients at risk of developing cardiovascular diseases and providing specialized care and treatment can reduce the risk of

Subjects

We enrolled 83 CKD patients who were treated in our hospital between June 2020 and June 2022 in this prospective cohort study. The diagnosis of CKD was established according to the clinical practice guideline for the evaluation and management of chronic kidney disease, as outlined by the KDIGO in 2012 [17]. Patients who were progressed to ESRD, had acute coronary syndrome or active infection, had received immunosuppressive, anti-infection, and anti-inflammatory drug treatments within the past

Frequency of T cell subtypes and cytokines of the patients

We collected serum samples from 83 patients with CKD and 80 healthy volunteers and detected the T cell subtypes and cytokines expression. We first analyzed the frequency of circulating LAG-3 and PD-1 expression on CD4+ and CD8+ T cells in different study groups. As shown in Fig. 1, the frequencies of LAG-3+PD-1+, LAG-3+ and PD-1+ cells were significantly increased in CKD patients compared to healthy volunteers (p < 0.05). ELISA results showed that patients with CKD had significantly elevated

Discussion

The progression of CKD can lead to anemia, osteoporosis, and cardiovascular diseases, and the 3-year survival rate for patients progressing to ESRD is less than 90% [20]. Early prediction and personalized treatment are crucial for slowing down disease progression and improving the prognosis of CKD patients. In this study, we discovered that high expression of the frequency of LAG-3+ and PD-1+ was a risk factor for the occurrence of MACE, while the frequency of CD4+ LAG-3+PD-1+ could be used to

Conclusion

In summary, our study revealed a significant increase in the frequencies of PD-1+ and LAG-3+ T cells in CKD patients. Furthermore, we found that the presence of CD4+ T cells expressing both PD-1+ and LAG-3+ could serve as a potential prognostic indicator for CKD patients. These findings offer novel insights and potential therapeutic targets for the management of CKD.

Ethics approval statement

This study was approved by the Ethics Committee of Affiliated Hospital of Jiangnan University (No. LS2021001).

Funding

None.

CRediT authorship contribution statement

Hongwei Jiang: Writing – review & editing, Writing – original draft, Resources, Project administration, Methodology, Formal analysis, Data curation, Conceptualization. Jing Wu: Software, Resources, Methodology, Investigation, Formal analysis, Data curation. Junlin Zhang: Visualization, Validation, Project administration, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We thank everyone, who supports us to finish this study.

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