{
  "abstract": "Objectives Tumour necrosis factor inhibitors (TNFi) are widely used and effective as treatment for immune-mediated inflammatory diseases (IMIDs). However, TNFi therapy causes a faster waning of antibody responses following vaccination. The underlying cause by which TNFi affect humoral immunity remains to be elucidated. The formation of long-lasting, high-affinity antibodies after vaccination results from germinal centre (GC)-derived, T cell-dependent B-cell responses. Therefore, this study investigated how TNFi affect the formation and maintenance of antigen-specific B- and CD4+ T-cell responses following SARS-CoV-2 mRNA vaccination.Methods SARS-CoV-2 spike-specific B-cell responses were characterised using spectral flow cytometry. Spike-specific CD4+ T cells were measured using an activation-induced marker assay. 15 patients with inflammatory bowel disease (IBD) treated with TNFi were compared with 9 IBD patients without systemic immunosuppression and 10 healthy controls.Results Spike-specific CD4+T-cell frequency and phenotype, including T follicular helper cells, were not affected by TNFi. Total spike-specific B-cell frequencies were reduced in TNFi-treated patients. Deep phenotyping revealed lower IgG+memory B-cell frequencies in TNFi-treated patients 3–6 months after vaccination. These data were confirmed in TNFi-treated rheumatoid arthritis patients. Interestingly, already at day 7 after the second vaccination, TNFi therapy reduced the induction of class-switched CD11c- CD71+activated B cells, which are believed to be GC-derived. Conversely, CD11c+B cells, associated with extrafollicular B-cell responses, were not affected by TNFi therapy.Conclusions These data suggest that TNFi therapy affects the differentiation of GC-derived B cells, which may explain its effect on humoral immune responses.",
  "authors": [
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands",
        "Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Laura YL Kummer"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Lisan H Kuijper"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands",
        "Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Laura Fernández Blanco"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Amélie Bos"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Christine Kreher"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Niels JM Verstegen"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Mariël C Duurland"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Veronique AL Konijn"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Tineke Jorritsma"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Maryse Tempert"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Charlotte Menage"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Maurice Steenhuis"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam UMC Location VUmc, Amsterdam, the Netherlands"
      ],
      "name": "Marit J van Gils"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Infection Prevention, Amsterdam UMC Location VUmc, Amsterdam, the Netherlands"
      ],
      "name": "Mathieu Claireaux"
    },
    {
      "affiliations": [
        "Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location VUmc, Amsterdam, the Netherlands"
      ],
      "name": "Juan J Garcia-Vallejo"
    },
    {
      "affiliations": [
        "Department of Gasteroenterology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Geert RAM D’Haens"
    },
    {
      "affiliations": [
        "Department of Gasteroenterology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Mark Löwenberg"
    },
    {
      "affiliations": [
        "Department of Gasteroenterology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Adriaan G Volkers"
    },
    {
      "affiliations": [
        "Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Koos PJ van Dam"
    },
    {
      "affiliations": [
        "Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Eileen W Stalman"
    },
    {
      "affiliations": [
        "Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands",
        "Department of Clinical Neurophysiology, St Antonius Ziekenhuis, Nieuwegein, the Netherlands"
      ],
      "name": "Luuk Wieske"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, Amsterdam, Netherlands"
      ],
      "name": "Sander W Tas"
    },
    {
      "affiliations": [
        "Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the Netherlands"
      ],
      "name": "Laura Boekel"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands",
        "Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, the Netherlands"
      ],
      "name": "Gertjan Wolbink"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Theo Rispens"
    },
    {
      "affiliations": [
        "Department of Pediatric Immunology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Taco W Kuijpers"
    },
    {
      "affiliations": [
        "Department of Neurology and Neurophysiology, Amsterdam UMC Location AMC, Amsterdam, the Netherlands"
      ],
      "name": "Filip Eftimov"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands",
        "Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands"
      ],
      "name": "S Marieke van Ham"
    },
    {
      "affiliations": [
        "Sanquin Research, Amsterdam, the Netherlands"
      ],
      "name": "Anja ten Brinke"
    }
  ],
  "title": "TNF inhibitors affect the induction and maintenance of spike-specific B-cell responses after mRNA vaccination",
  "uid": "6394a92e-3a0d-5c19-83e9-5912ce95cc18"
}