Elevated checkpoint inhibitor expression and Treg cell number in autosomal dominant polycystic kidney disease and their correlation with disease parameters and hypertension

• Published in: Clinical and experimental medicine 2023-11, Vol.23 (7), p.3631-3640
• Main Authors: Sahin, Ali, Kocyigit, Ismail, Aslan, Kubra, Eroglu, Eray, Demiray, Alparslan, Eken, Ahmet
• Format: Article
• Language: English
• Subjects: CD3 antigen; CD4 antigen; CD8 antigen; Cell number; CTLA-4 protein; Flow cytometry; Glomerular filtration rate; Hematology; Hypertension; Immune checkpoint inhibitors; Internal Medicine; Kidney diseases; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Oncology; PD-1 protein; Peripheral blood; Phenotypes; Phenotyping; Polycystic kidney; Risk factors; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1591-9528; 1591-8890; 1591-9528
• DOI: 10.1007/s10238-023-01031-2

Autosomal dominant polycystic kidney disease (ADPKD) has cancer-like pathophysiology. In this study, we aimed to investigate the phenotype of peripheral blood (PB) T cell subsets and immune checkpoint inhibitor expression of ADPKD patients across different chronic kidney disease (CKD) stages. Seventy-two patients with ADPKD and twenty-three healthy controls were included in the study. The patients were grouped into five different CKD stages, according to glomerular filtration rate (GFR). PB mononuclear cells were isolated and T cell subsets and cytokine production were examined by flow cytometry. CRP levels, height-adjusted total kidney volume (htTKV), rate of hypertension (HT) differed significantly across different GFR stages in ADPKD. T cell phenotyping revealed significantly elevated CD3+ T cells, CD4+, CD8+, double-negative, and double-positive subsets and significantly elevated IFN-γ and TNF-α producing subsets of CD4+, CD8+ cells. The expression of checkpoint inhibitors CTLA-4, PD-1, and TIGIT by T cell subsets was also increased to various extent. Additionally, Treg cell numbers and suppressive markers CTLA-4, PD-1, and TIGIT were significantly elevated in ADPKD patients’ PB. Treg CTLA4 expression and CD4CD8DP T cell frequency in patients with HT were significantly higher. Lastly, HT and increased htTKV and higher frequency of PD1+ CD8SP were found to be risk factors for rapid disease progression. Our data provide the first detailed analyses of checkpoint inhibitor expression by PB T cell subsets during stages of ADPKD, and that a higher frequency of PD1+ CD8SP cells is associated with rapid disease progression.