{
  "abstract": "Objectives Systemic lupus erythematosus (SLE) is characterized by B cell-driven autoimmunity and an upregulation of type I Interferon (IFN). IgG antibodies carry an N-glycosylation site (Asn297) occupied by different types of glycans, which affects effector functions of IgG. This project aimed to determine what drives changes in Fc glycosylation profiles of IgG in SLE.Methods Total IgG was purified by affinity purification from the serum of healthy donors and SLE patients as well as from paired SLE patient samples before and after CD19-CAR T cell therapy. B cell subsets and induced plasma cells were sorted and cultured in vitro with various stimuli. Secreted IgG from supernatant was purified, and Fc-glycosylation profiles were determined by Liquid Chromatography-Mass Spectrometry (LC-MS).Results Our results revealed a low degree of Fc-galactosylation in total IgG from SLE patients compared with HD which strongly correlated to total IgG serum levels. CD19-CAR T cell treatment led to normalization of IgG galactosylation, coinciding with decreases in the type I IFN signature. As we previously showed a correlation between hypergammaglobulinemia and type I IFN in SLE, we next investigated the relationship between IFN and galactosylation. Therefore, we cultured B cells or plasma cells in vitro with or without type I IFN, and revealed that, depending on the culture conditions, type I IFN can decrease galactosylation in B cells.Conclusions Taken together, our results suggest a role for type I IFN in modulating the galactosylation of IgG. Given the role of glycosylation on IgG effector functions such as complement activation, the cytokine environment may have profound effects on inflammatory responses in SLE that can be reverted following CD19-CAR T cell therapy.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Huihong Wen"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Hugo Van Dooren"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Jacqueline Dekkers"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Karin Van Schie"
    },
    {
      "affiliations": [
        "Department of Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitä, Erlangen, Germany"
      ],
      "name": "Luis E Muñoz"
    },
    {
      "affiliations": [
        "Department of Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitä, Erlangen, Germany"
      ],
      "name": "Ulrike Steffen"
    },
    {
      "affiliations": [
        "Department of Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitä, Erlangen, Germany"
      ],
      "name": "Georg Schett"
    },
    {
      "affiliations": [
        "Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Leiden, The Netherlands"
      ],
      "name": "Manfred Wuhrer"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "René Em Toes"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Jolien Suurmond"
    }
  ],
  "title": "PO:06:158 Regulation of IgG glycosylation in systemic lupus erythematosus",
  "uid": "10cdfa6c-7367-51de-adab-1c95bdfda1ed"
}