{
  "abstract": "Objectives SLE is predominantly a B-cell driven disease in which autoreactive B cells exhibit defective tolerance checkpoints, leading to abnormal selection and survival of potentially pathogenic clones. To date, the precise characteristics and functions of autoreactive B cells remain elusive. We aimed to profile B-cell phenotypes associated with autoimmunity by investigating the expression of CD72, a C-type lectin and checkpoint molecule, together with the activation marker and death receptor CD95. We further examined the functional and transcriptomic features of CD72-negative B cells to better understand their role in lupus pathogenesis.Methods Twenty-four SLE patients, including 20 with active disease (SLEDAI-2K > 4), were evaluated. In the active group, nine had lupus nephritis (LN) and seven received rituximab treatment with samples collected at baseline and follow-up at 3 and 6 months. B-cell phenotypes and functions were analyzed using full-spectrum flow cytometry, and correlation analyses were performed. Immunoglobulin production was studied in vitro. Transcriptomic profiling was performed by bulk RNA-sequencing analysis.Results Active SLE patients showed marked downregulation of CD72 on non-naïve CD19+B-cell subsets compared to inactive patients and healthy controls (HC) paralleled by CD95 expression. Such CD72-CD95+B cells were enriched in plasmablast (20%), switched-memory (50%) and double negative 2 (30%) cell populations. CD72-CD95+B cells were also characterized by CD20 downregulation. Transcriptomic profiling of lupus CD72-CD95+B cells revealed an upregulation of genes associated with B-cell activation, proliferation and differentiation. Functionally, lupus CD72-CD95+B cells displayed increased SYK- and ERK- phosphorylation following BCR stimulation, as compared to the same subset in HC and to overall CD19+B cells. Upon in vitro stimulation, CD72-CD95+B cells produced high levels of immunoglobulin G (IgG), confirming their capacity to become antibody-producing cells. Clinically, the frequency of CD72-CD95+B cells positively correlated with disease activity as measured by SLEDAI-2K (r=0.6, p=0.02). Notably, this cell phenotype remained detectable during the B-cell depletion phase of RTX-treated patients.Conclusions Expanded CD72-CD95+B cells in SLE display an activated phenotype supported by transcriptomic evidence of enhanced B-cell activation and differentiation toward antibody secreting cells. Their association with disease activity suggests a contribution to disease. Persistence after anti-CD20 therapy suggests potential resilience to this treatment modality.",
  "authors": [
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Kittikorn Wangriatisak"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Wenqi Huang"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Salim Ghannoum"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Giorgio Sechi"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Sofia Zachari"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden",
        "Centre for Rheumatology, Academic Specialist Centre, Stockholm Region, Sweden, Stockholm, Sweden"
      ],
      "name": "Vilija Oke"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Karine Chemin"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Caroline Grönwall"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Iva Gunnarsson"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Vivianne Malmström"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Swe, Stockholm, Sweden"
      ],
      "name": "Francesca Faustini"
    }
  ],
  "title": "PO:01:002 Profiling the CD72-CD95+B-cell phenotype in SLE: integrating molecular and functional features with clinical parameters and treatment responses",
  "uid": "5dfe0404-f38e-515a-8289-acd071f9fb57"
}