{
  "abstract": "Objective B-cell activating factor (BAFF) is essential for B-cell survival and innate immune activation, and its dysregulation contributes to the pathogenesis of lupus nephritis (LN). This study investigated whether BAFF-pathway inhibition alters the balance between regulatory B cells (Bregs) and type 1 innate lymphoid cells (ILC1s) in paediatric LN.Methods In this prospective, open-label randomised study, 60 paediatric patients with biopsy-confirmed class III/IV LN were randomised to standard therapy (mycophenolate mofetil and corticosteroids; n=30) or standard therapy plus the belimumab (10 mg/kg intravenously every 4 weeks for 6 months; n=30). Ten healthy children and three patients with biopsy-confirmed minimal change disease served as controls. Flow cytometry quantified IL-10-producing Bregs and circulating ILC1s. Clinically indicated paired renal biopsies (n=3) underwent transcriptomic and immunofluorescence analyses.Results Belimumab was associated with greater increases in serum C3, reductions in antidouble-stranded DNA titres, decreased proteinuria, improved Systemic Lupus Erythematosus Disease Activity Index 2000 scores and reduced corticosteroid exposure. Belimumab expanded memory B cells and IL-10-producing CD19 +CD5+ and CD19+CD24hi+CD38hi+ Bregs, with enhanced suppression of CD4+ T cell proliferation. Treatment reduced circulating and renal ILC1s, downregulated interferon (IFN)-stimulated genes and modulated inflammatory pathways. Serum cytokine profiling showed decreased IFN-γ, interleukin (IL)-17A, IL-10 and BAFF levels, alongside increased IL-35. Phosphorylation of the aryl hydrocarbon receptor and signal transducer and activator of transcription 3 (STAT3) in Bregs was partially restored.Conclusions BAFF inhibition in paediatric LN is associated with rebalancing of innate and adaptive immunity through enhancement of Breg function and suppression of ILC1-driven inflammation.",
  "authors": [
    {
      "affiliations": [
        "Clinical Immunological Center, China Medical University Hospital, Taichung City, Taiwan",
        "Division of Pediatric Nephrology, China Medical University Children’s Hospital, Taichung City, Taiwan"
      ],
      "name": "Ching-Yuang Lin"
    },
    {
      "affiliations": [
        "Division of Pediatric Nephrology, China Medical University Children’s Hospital, Taichung City, Taiwan"
      ],
      "name": "Jien-Wen Chien"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Changhua Christian Children’s Hospital, Changhua, Taiwan",
        "Institute of Biomedical Sciences, National Chung Hsing University, Taichung City, Taiwan"
      ],
      "name": "Kan-Hsuan Lin"
    },
    {
      "affiliations": [
        "Department of Allergy, Immunology and Rheumatology, Changhua Christian Hospital, Changhua, Taiwan"
      ],
      "name": "Kai-Hung Hsiao"
    },
    {
      "affiliations": [
        "Department of Allergy, Immunology and Rheumatology, Changhua Christian Hospital, Changhua, Taiwan"
      ],
      "name": "Ya-Chih Tien"
    },
    {
      "affiliations": [
        "Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan"
      ],
      "name": "Tzu-Cheng Su"
    },
    {
      "affiliations": [
        "Division of Pediatric Nephrology, China Medical University Children’s Hospital, Taichung City, Taiwan",
        "Division of Allergy, Immunology and Rheumatology, China Medical University Children’s Hospital, Taichung City, Taiwan",
        "School of Medicine, China Medical University, Taichung City, Taiwan"
      ],
      "name": "Chang-Ching Wei"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, Taiwan",
        "Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan"
      ],
      "name": "Lin-Shien Fu"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Mackay Memorial Hospital, New Taipei City, Taiwan",
        "Department of Microbiology & Immunology, National Defense Medical University, Taipei, Taiwan",
        "Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"
      ],
      "name": "Kuender D Yang"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Changhua Christian Children’s Hospital, Changhua, Taiwan",
        "Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan",
        "Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan",
        "Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung City, Taiwan"
      ],
      "name": "Jun-Kai Kao"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Changhua Christian Children’s Hospital, Changhua, Taiwan",
        "Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, Taiwan",
        "School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan",
        "School of Medicine, Chung Shan Medical University, Taichung City, Taiwan"
      ],
      "name": "Yi-Giien Tsai"
    }
  ],
  "title": "Regulatory B cell expansion and type 1 innate lymphoid cell suppression characterise immune modulation in paediatric lupus nephritis",
  "uid": "0132805b-cdc9-5524-9f52-aceca226fd02"
}