{
  "abstract": "Objectives Belimumab (BEL) is an IgG1 antibody against the soluble form of B-cell activating factor (BAFF). BAFF has a crucial role in B-cell survival of specific subsets. Although BEL, in combination with standard of care, has shown good treatment efficacy in systemic lupus erythematosus (SLE) patients with and without renal involvement, new onset of lupus nephritis (LN) during BLM treatment was reported in subjects without prior history of LN. Since SLE patients have displayed rapid reductions of IL-10 after initiation of BEL therapy, we hypothesise that BAFF inhibition may lead to a reduced frequency or function of IL-10-producing regulatory B-cells. Objective: To investigate whether, and how, BEL treatment affects the development and function of regulatory B-cells.Methods B and T cells were isolated from SLE patient and matched healthy controls. B-cells were cultured with multiple stimuli including BAFF and BEL to measure IL-10 and IL-6 production in supernatants with ELISA to evaluate their regulatory capacity by IL-10/IL-6 ratio. Also, these conditions were tested in coculture with activated T-cells stained with carboxyfluorescein succinimidyl ester (CFSE) for 4 days to assess the inhibition of proliferation and the cytokine production in supernatants (IFN-y and IL-10) as a means of evaluating the regulatory function of the B-cells.Results In healthy controls, BAFF showed an additive effect in IL-10 production from cultured B-cells in combination with CpG-B, CD40L, and IL-21. Although BAFF alone or in the already mentioned combination of stimuli did not show a significant impact on the inhibition of T-cell proliferation in coculture assays, it caused reduction of IFN-y production. As expected, BEL was effective in neutralising BAFF’s effect in cultured B-cells and in coculture with T-cells.Conclusions BAFF appears to enhance regulatory properties of B-cells in some conditions, suggesting that certain doses of BEL may suppress this regulatory support. However, since regulatory B-cells in SLE are known to display defective function, the precise role of BAFF in modulating regulatory B-cells in SLE remains to be elucidated. A better understanding of the impact of BEL on regulatory B-cells may pave the way for patient-tailored dosage schemes and early treatment assessment of B-cell-targeted therapies.",
  "authors": [
    {
      "affiliations": [
        "Linköping University – Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Jhonatan Antonio Alvarez Gomez"
    },
    {
      "affiliations": [
        "Linköping University – Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Tomas Walhelm"
    },
    {
      "affiliations": [
        "Linköping University – Department of Health, Medicine and Caring Sciences, Linköping, Sweden"
      ],
      "name": "Daniel Appelgren"
    },
    {
      "affiliations": [
        "Karolinska Institutet – Department of Medicine Solna, Stockholm, Sweden"
      ],
      "name": "Ioannis Parodis"
    },
    {
      "affiliations": [
        "Linköping University – Department of Biomedical and Clinical Sciences, Linköping, Sweden"
      ],
      "name": "Christopher Sjöwall"
    }
  ],
  "title": "PO:08:223 BAFF in systemic lupus erythematosus – A double-edged sword?",
  "uid": "1b499b7d-829e-555b-9798-cf9642ea463c"
}