Circulating cd14++cd16(+) monocytes, nk cells and lymphocyte subsets correlate with conventional and novel deformation related indices of left ventricular function in kidney transplant recipients with no established cardiovascular disease

Abstract BACKGROUND AND AIMS Kidney transplant recipients (KTRs) carry a significant burden of cardiovascular disease (CVD), despite improvement of patterns of left ventricular (LV) remodeling following kidney transplantation. Kidney allograft dysfunction and the immunosuppressed milieu play a major adverse role in myocardial structural changes in asymptomatic KTRs. An intricate relationship exists between immune system responses with heart failure syndromes, manifesting among others with aberrant activity and counts of proinflammatory CD16+monocytes, of natural killer (NK) cells and T regulatory cells (Tregs). The associations of immune cell subpopulations with subclinical markers of CVD remain to be determined in KTRs. The aim of our study was to investigate potential correlations between blood levels of specific immune cells subsets with conventional and novel deformation related indices of LV function in KTRs. METHOD 31 stable KTRs (mean age 58 ± 9.28 years, 67% males, 13% diabetics) without established CVD were enrolled. Control population included 17 chronic kidney disease (CKD) stage 3 patients without history of CVD. Additional exclusion criteria were history of malignancy, autoimmune disease and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+B lymphocytes, CD3+CD4+T cells, CD3+CD8+T cells and Tregs (CD4+CD25+FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry. Simultaneously, conventional (left atrial volume index (LAVI), LV mass index (LVMI), E/E’) and novel 2D speckle tracking (2DST) echocardiographic indices of LV function [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), TWIST AND UNTWIST] were assessed. RESULTS KTRs had a mean eGFR of 58 ± 18 mL/min/1.73 m2 (CKD-EPI) and mean 24-h proteinuria (PER) 707 ± -1185 mg/24 h. Total lymphocytes, B-cells, T-cells and CD8+T cells counts correlated positively with eGFR (P < 0.05). Increased non-classical CD14+CD16++ monocytes were associated with proteinuria levels (P < 0.01) whereas an inverse correlation was observed between the percentage of classical CD14++CD16- monocytes with PER (P < 0.05). When compared with CKD patients, KTRs displayed higher CD14++CD16- and lower CD14+CD16++ monocytes counts, a lower percentage of NK cells and T cells and lower Tregs (significant differences presented in Table 1). Regarding classical indices of LV function, increased total monocytes were associated with elevated LAVI (P < 0.05), whereas an increased percentage of the intermediate CD14++CD16+monocytes correlated positively with an increased E/E’ value. Increased NK cells were associated with more negative GCS values (P < 0.05). No significant correlations were observed between the rest immune cells with the classical or novel LV dysfunction indices. CONCLUSION Alterations of immune cells subsets correlate with subclinical markers of LV dysfunction in KTRs with no established CVD. Future research is required to evaluate the role of immune subpopulations as tools to identify KTRs who are at the highest risk for complications and guide interventions.