Influence of end stage renal disease on CD28 expression and T-cell immunity.

BACKGROUND: T-cell immunity is affected in end stage renal disease (ESRD). However, whether this happens at pre- or post-dialysis stage and what is the impact of different renal replacement methods, remains unclear. We investigated the alterations of T-cell subtypes in patients at pre-dialysis ESRD and their further changes during dialysis. METHODS: CD4+, CD8+, CD4 + CD28null and CD8 + CD28null T-cells were analysed in 40 ESRD patients at two different time points, (a) the day started on dialysis (ESRD-T0) and (b) 6 months later (ESRD-T6), while being on haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Twenty-five age matched healthy volunteers served as controls. RESULTS: CD4+ and CD8+ T-cells were significantly reduced in ESRD-T0 patients compared to controls, 604 (105-3551) vs 943 (584-1867)µ/L, P = .001, and 352 (103-1561) vs 422.4 (263-1453)µ/L, P = .05, respectively. However, proportions of CD4 + CD28null and CD8 + CD28null cells were significantly increased, 6.4 (0.3-30)% vs 2.7 (0.1-7.8)%, P = .04 and 58.2 (12.8-85.4)% vs 39 (7.8-57.1)%, P = .01, respectively. Proportion of CD4 + CD28null cells showed significant correlation with serum CRP (r = .4, P = .04) and albumin levels (r = -.5, P = .007) in ERSD patients. ESRD-T0 patients with cardiovascular disease (CVD) had increased CD4 + CD28null and CD8 + CD28null proportions, 8.6 (1-30)% vs 2.1 (0.1-19.8)%, P = .04 and 62.5 (12.8-85.4)% vs 45.5 (5.7-73.7)%, P = .02, respectively, compared to those without. Six months later, both CD4 + CD28null and CD8 + CD28null T-cells were increased in HD compared to CAPD patients, by +110.11 (-27.1 to 311.4)% vs -28.1 (-100 to 30)%, P = .003 and +55.23 (-29.06 to 197.93)% vs -8.34 (-54.99 to 66.72)%, P = .05, respectively. CONCLUSIONS: CD4 + CD28null and CD8 + CD28null T-cells are increased at pre-dialysis ESRD, and correlate with chronic inflammatory markers and the presence of CVD. Dialysis methods seem to have different impact on these subpopulations.

Humoral and Cellular Immunity Are Significantly Affected in Renal Transplant Recipients, following Vaccination with BNT162b2.

BACKGROUND: Renal transplant recipients (RTRs) tend to mount weaker immune responses to vaccinations, including vaccines against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Humoral immunity was assessed using anti-receptor binding domain (RBD) and neutralizing antibodies (NAb) serum levels measured by ELISA, and cellular immunity was assessed using T-, B-, NK, natural killer-like T (NKT)-cell subpopulations, and monocytes measured by flow cytometry, and also specific T-cell immunity, at predefined time points after BNT162b2 vaccination, in 57 adult RTRs. RESULTS: Administration of three booster doses was necessary to achieve anti-RBD and NAb protective levels in almost all patients (92.98%). Ab production, at several time points, was positively correlated with the corresponding renal function and inversely correlated with hemodialysis vintage (HDV) and treatment with mycophenolic acid (MPA). A gradual rise in several cell subpopulations, including total lymphocytes (p = 0.026), memory B cells (p = 0.028), activated CD4 (p = 0.005), and CD8 cells (p = 0.001), was observed even after the third vaccination dose, while a significant reduction in CD3+PD1+ (p = 0.002), NKT (p = 0.011), and activated NKT cells (p = 0.034) was noted during the same time interval. Moreover, SARS-CoV-2-specific T-cells were present in 41% of the patients who were unable to develop Nabs, and their positivity rates four months after the second dose were in inverse correlation with monocytes (p = 0.045) and NKT cells (p = 0.01). CONCLUSIONS: SARS-CoV-2-specific T-cell responses preceded the humoral ones, while two booster doses were needed for this group of immunocompromised patients to mount a protective immune response.