Poly-IgA immune complex as a monitoring biomarker of response to telitacicept in IgA nephropathy

Front Immunol. 2026 May 29:17:1751549. doi: 10.3389/fimmu.2026.1751549. eCollection 2026.

Abstract

Background: Immunoglobulin A nephropathy (IgAN) is a common immune-mediated kidney disease. Its pathogenesis involves dysregulated B cell activation, excessive production of galactose-deficient immunoglobulin A1 (Gd-IgA1), and formation of IgA immune complex, which collectively drive glomerular injury. Telitacicept, a fusion protein that blocks B cell activation pathways, may counteract these mechanisms, but observational data and reliable biomarkers of therapeutic response remain limited.

Objective: This study aimed to evaluate the clinical efficacy and safety of telitacicept and to determine whether changes in circulating B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and Poly-IgA immune complex (Poly-IgA) reflect treatment response.

Methods: In this single-center retrospective cohort study, 38 adult patients with IgAN received telitacicept combined with low-dose glucocorticoids for up to 9 months. Clinical outcomes, renal function, and safety events were monitored longitudinally, and serum biomarkers were analyzed to assess associations with remission.

Results: Telitacicept treatment resulted in a substantial and sustained reduction in proteinuria while maintaining stable renal function, with over half of patients achieving complete or partial remission at 3 months. All three biomarkers reduced with treatment, and Poly-IgA showed the strongest correlation with clinical remission and the best ability to distinguish remission from non-remission.

Conclusion: Telitacicept is an effective and well tolerated drug in the treatment of IgAN, with immunomodulatory effects consistent with suppression of pathogenic B cell activity. The lower level of Poly-IgA during treatment is significantly associated with clinical remission.It may serve as a promising biomarker for monitoring treatment response in the future, supporting its potential use in guiding individualized therapy for patients with IgAN.

Keywords: APRIL; BAFF; IgA nephropathy; Poly-IgA; biomarker; telitacicept.

MeSH terms

  • Adult
  • Antigen-Antibody Complex* / blood
  • Antigen-Antibody Complex* / immunology
  • B-Cell Activating Factor / blood
  • Biomarkers / blood
  • Female
  • Glomerulonephritis, IGA* / blood
  • Glomerulonephritis, IGA* / diagnosis
  • Glomerulonephritis, IGA* / drug therapy
  • Glomerulonephritis, IGA* / immunology
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulin A* / blood
  • Immunoglobulin A* / immunology
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / blood

Substances

  • Antigen-Antibody Complex
  • Biomarkers
  • Immunoglobulin A
  • B-Cell Activating Factor
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • polymeric IgA
  • TNFSF13B protein, human
  • Recombinant Fusion Proteins
  • Glucocorticoids
  • TNFSF13 protein, human
  • telitacicept