BACKGROUND: Stage 5 chronic kidney disease (CKD5) is linked to complex yet not fully understood disturbances in immune system. This study aimed to investigate these disturbances by exploring the detailed composition of peripheral blood immune cell compartments in CKD5 patients and to provide integrative, multivariable dissection of how common inflammatory risk factors shape the immune landscape. METHODS: This cross-sectional study included 107 patients with chronic kidney disease stage 5 (CKD5) and 29 healthy blood donors as controls. Peripheral blood B cells, T cells, and dendritic cells were measured using a standardized and validated flow cytometry panel. The impact of selected clinical factors on immune cell composition was initially evaluated using a robust multivariate method (PERMANOVA). Variables that significantly affected immune cell composition were then included in a subsequent series of Poisson regression models, assessing predictors influence on the counts of individual immune cell subpopulations. RESULTS: Compared to healthy controls, CKD5 patients presented with B cell lymphopenia across all measured subsets except for plasmablasts, T cell lymphopenia with an immunosenescent phenotype predominantly in the CD4+ compartment, and significantly higher counts of LIN-HLA-DR+ antigen-presenting cells, mainly due to an increase in myeloid dendritic cell subpopulations. PERMANOVA identified smoking, CMV seropositivity, age, dialysis treatment, and atherosclerotic cardiovascular disease as factors significantly influencing peripheral blood immune composition. Subsequent Poisson regression models revealed that smoking was associated mainly with an increase in switched memory B cells, CMV seropositivity with an increase in CD4+ and CD8+ TEMRA cells, age with a decrease in naive CD8+ T cells, and dialysis treatment with an increase in marginal-zone B cells. CONCLUSIONS: Patients with CKD5 exhibit distinct composition of peripheral blood immune cells, further modified by other factors associated with systemic inflammatory response. These factors should be considered in immunomonitoring protocols and may enhance prediction of clinical outcomes such as vaccine responses.

• Klíčová slova
• B cells, T cells, chronic kidney disease, dendritic cells, flow cytometry, inflammation, peripheral blood immune cell composition,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. METHODS: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. RESULTS: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. CONCLUSIONS: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).

• Publikační typ
• časopisecké články MeSH