Th1-dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses
Yvette den Hartog,
S. Reshwan K. Malahe,
Wim J. R. Rietdijk,
Marjolein Dieterich,
Lennert Gommers,
Daryl Geers,
Susanne Bogers,
Debbie van Baarle,
Dimitri A. Diavatopoulos,
A. Lianne Messchendorp,
Renate G. van der Molen,
Ester B. M. Remmerswaal,
Frederike J. Bemelman,
Ron T. Gansevoort,
Luuk B. Hilbrands,
Jan-Stephan Sanders,
Corine H. GeurtsvanKessel,
Marcia M. L. Kho,
Marlies E. J. Reinders,
Rory D. de Vries,
Carla C. Baan,
on behalf of RECOVAC Consortium
Affiliations
Yvette den Hartog
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center
S. Reshwan K. Malahe
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center
Wim J. R. Rietdijk
Department of Hospital Pharmacy, University Medical Center
Marjolein Dieterich
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center
Lennert Gommers
Department of Viroscience, University Medical Center
Daryl Geers
Department of Viroscience, University Medical Center
Susanne Bogers
Department of Viroscience, University Medical Center
Debbie van Baarle
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen
Dimitri A. Diavatopoulos
Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen
A. Lianne Messchendorp
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen
Renate G. van der Molen
Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen
Ester B. M. Remmerswaal
Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam
Frederike J. Bemelman
Renal Transplant Unit, Amsterdam UMC, University of Amsterdam
Ron T. Gansevoort
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen
Luuk B. Hilbrands
Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences
Jan-Stephan Sanders
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen
Corine H. GeurtsvanKessel
Department of Viroscience, University Medical Center
Marcia M. L. Kho
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center
Marlies E. J. Reinders
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center
Rory D. de Vries
Department of Viroscience, University Medical Center
Carla C. Baan
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center
Abstract Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4+ and CD8+ memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)1 (IL-2, TNF-α, and IFN-γ) and Th2 (IL-4, IL-5, IL-13) cytokines, and low levels of Th17 (IL-17A, IL-22) and Th9 (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th1 cytokines upon re-stimulation, with lower levels or absence of Th2, Th17, and Th9 cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th1 and Th2 cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.