AUTHOR=Darbouret- Hervier Anne , Assi Nada , Asensio Marie-Jeanne , Bernabe Beatrice , Lechevallier Aurélie , Iantomasi Raffaella , Rokbi Bachra , Botelho-Nevers Elisabeth , Ruiz Sophie 

TITLE=Anti-staphylococcus aureus adaptive immunity is impaired in end-stage renal disease patients on hemodialysis: one-year longitudinal study

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1123160

DOI=10.3389/fimmu.2023.1123160

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Patients with end-stage renal disease (ESRD) display defects in adaptive and innate immunity, increasing susceptibility to infection. <italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) is a major cause of bacteraemia in this population and is associated with increased mortality. More information on the immune response to <italic>S. aureus</italic> in these patients is needed to inform effective vaccine development.</p></sec><sec><title>Methods</title><p>A longitudinal prospective study was carried out at two medical centers and included 48 ESRD patients who started chronic hemodialysis (HD) treatment ≤3 months before inclusion. Control samples were taken from 62 consenting healthy blood donors. Blood samples were obtained from ESRD patients at each visit, on month (M) 0 (beginning of HD), M6 and M12. Around 50 immunological markers of adaptive and innate immunity were assessed to compare immune responses to <italic>S. aureus</italic> in ESRD patients versus controls to document the changes on their immune profile during HD.</p></sec><sec><title>Results</title><p><italic>S. aureus</italic> survival in whole blood was significantly higher in ESRD patients than in controls at M0 (<italic>P</italic>=0.049), while impaired oxidative burst activity was observed in ESRD patients at all timepoints (<italic>P</italic>&lt;0.001). <italic>S. aureus</italic>-specific immunoglobulin G (IgG) responses to iron surface determinant B (IsdB) and <italic>S. aureus</italic> α hemolysin (Hla) antigens were lower in ESRD patients than in healthy donors at M0 (<italic>P</italic>=0.003 and <italic>P</italic>=0.007, respectively) and M6 (<italic>P</italic>=0.05 and <italic>P</italic>=0.03, respectively), but were restored to control levels at M12. Moreover, <italic>S. aureus</italic>-specific T-helper cell responses were comparable to controls for IsdB but were impaired for Hla antigen at all timepoints: 10% of ESRD patients responded to Hla at M0, increasing to 30% at M12, compared with 45% of healthy donors. B-cell and T-cell concentrations in blood were significantly reduced (by 60% and 40%, respectively) compared with healthy controls. Finally, upregulation of Human Leucocyte Antigen-DR (HLA-DR) and C-C chemokine Receptor type 2 (CCR2) was impaired at M0 but was restored during the first year of HD.</p></sec><sec><title>Conclusion</title><p>All together, these results show that adaptive immunity was largely impaired in ESRD patients, whereas innate immunity was less impacted and tended to be restored by HD.</p></sec>