The role of interleukin-21 in COVID-19 vaccine–induced B cell–mediated immune responses in patients with kidney disease and kidney transplant recipients

S. Reshwan K. Malahe, Yvette den Hartog, RECOVAC Consortium / RECOVAC Collaborators, Wim J.R. Rietdijk, Debbie van Baarle, Ronella de Kuiper, Derek Reijerkerk, Alicia M. Ras, Daryl Geers, 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, Rory D. de VriesMarlies E.J. Reinders, Carla C. Baan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

T-cell–mediated help to B cells is required for the development of humoral responses, in which the cytokine interleukin (IL)-21 is key. Here, we studied the mRNA-1273 vaccine–induced SARS-CoV-2–specific memory T-cell IL-21 response, memory B cell response, and immunoglobulin (Ig)G antibody levels in peripheral blood at 28 days after the second vaccination by ELISpot and the fluorescent bead–based multiplex immunoassay, respectively. We included 40 patients with chronic kidney disease (CKD), 34 patients on dialysis, 63 kidney transplant recipients (KTR), and 47 controls. We found that KTR, but not patients with CKD and those receiving dialysis, showed a significantly lower number of SARS-CoV-2–specific IL-21 producing T cells than controls (P < .001). KTR and patients with CKD showed lower numbers of SARS-CoV-2–specific IgG–producing memory B cells when compared with controls (P < .001 and P = .01, respectively). The T-cell IL-21 response was positively associated with the SARS-CoV-2–specific B cell response and the SARS-CoV-2 spike S1–specific IgG antibody levels (both Pearson r = 0.5; P < .001). In addition, SARS-CoV-2–specific B cell responses were shown to be IL-21 dependent. Taken together, we show that IL-21 signaling is important in eliciting robust B cell–mediated immune responses in patients with kidney disease and KTR.

Original languageEnglish
Pages (from-to)1411-1424
Number of pages14
JournalAmerican Journal of Transplantation
Volume23
Issue number9
Early online date1 Jun 2023
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Funding Information:
The Dutch Renal patients COVID-19 VACcination (RECOVAC) study was funded by the Netherlands Organization for Health Research and Development (ZonMw; project number: 10430072010002 ) and the Dutch Kidney foundation (project number: 21OP+036 ). These organizations had no role in the design of the study, data interpretation, writing of the manuscript, or decision to submit the manuscript.

Publisher Copyright:
© 2023 The Author(s)

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