Higher Proinflammatory Cytokines Are Associated With Increased Antibody Titer After a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients

Transplantation. 2022 Apr 1;106(4):835-841. doi: 10.1097/TP.0000000000004057.

Abstract

Background: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if prevaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination.

Methods: A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, and comparison to 16 healthy controls (HCs). Antispike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detection-based multiplexed sandwich immunoassays (Meso Scale Diagnostics) were used to quantify plasma cytokine and chemokine concentrations (n = 20 analytes) and compare concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine using Wilcoxon-rank-sum test with false discovery rates computed to correct for multiple comparisons.

Results: In the study population, 100% of HCs, 59% of SOTRs after 2 doses and 63% of SOTRs after 3 doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in baseline cytokine levels between SOTRs with high versus low-titer antibodies after 2 doses of vaccine. However, as compared with poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher prethird dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1α, and TNF-α (false discovery rates < 0.05).

Conclusions: A specific inflammatory profile may be associated with developing higher antibodies in response to a third dose of SARS-CoV-2 vaccine in SOTRs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • COVID-19 Vaccines / adverse effects
  • COVID-19* / prevention & control
  • Cross-Sectional Studies
  • Cytokines
  • Humans
  • Organ Transplantation* / adverse effects
  • SARS-CoV-2
  • Transplant Recipients
  • Vaccines, Synthetic
  • mRNA Vaccines

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Cytokines
  • Vaccines, Synthetic
  • mRNA Vaccines