Kidney Week

Abstract: TH-PO0430

B Regulatory Cells: An Unintended Target of New Anti-B-Cell Therapies in IgAN?

Session Information

• Glomerular Diseases: Autoimmune Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Nguyen, Victoria V., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Victoria V. Nguyen, MD

• Fernandez, Loreto, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Loreto Fernandez, PhD

• Chen, Dhruti P., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Dhruti P. Chen, MD, FASN

• Falk, Ronald, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Ronald Falk, MD, FASN

• Saha, Manish K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Manish K. Saha, MD

• McKee, Sarah L., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Sarah L. McKee

• Hogan, Susan L., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Susan L. Hogan, PhD, MPH

• Derebail, Vimal K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Vimal K. Derebail, MD, MPH, FASN

• Hu, Yichun, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Yichun Hu

• Bunch, Donna O., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Donna O. Bunch, PhD

Background

B cells plays an integral part in pathogenesis of IgA Nephropathy (IgAN). Regulatory B cells (Bregs) play a significant role in suppressing autoimmune responses. A proliferation inducing ligand (APRIL) induces IL-10 production, a defining anti-inflammatory cytokine of Bregs. While new therapies targeting APRIL show promising results in patients with IgAN, they could target beneficial Bregs in addition to pathogenic B cells.

Methods

Peripheral blood mononuclear cells from patients with biopsy-proven IgAN off immunosuppression were included. Based on CureGN criteria of disease activity, we compared 21 active, 10 remission, and 9 healthy controls (HC) to evaluate TACI and IgA expression on Bregs (CD19⁺CD24^hiCD38^hi), memory B cells (CD19⁺CD24^hiCD38^lo), switched memory (IgD^negCD27⁺), and plasmablasts (CD19⁺CD24^negCD38^hi) using spectral flow cytometry. Data were analyzed in FlowJo and medians reported. Groups were compared using a non-parametric Kruskal-Wallis test followed by Dunn’s correction for multiple testing

Results

Patients with IgAN had significantly more switched memory cells (17%, 15%), IgA⁺ plasmablasts (50%, 50%), and TACI⁺IgA⁺ plasmablasts (40%, 37%) in active disease and remission respectively than HCs (7%, 4%, 13%; p values shown in Figure 1). Total B regs trended higher (6.1%, p=0.077) in active IgAN relative to HCs (3.6%). IgA⁺Bregs trended higher in both active (2.3%) and remission (1.9%) compared to HC. IgAN patients had higher TACI⁺IgA⁺ Bregs in active disease (1.6%, p=0.015) and remission (1.7%) than HCs (0.3%).

Conclusion

Immunophenotyping of patients with IgAN indicates differentiation toward class-switched memory cells and antibody producing cells consistent with autoimmune disease. An upregulation of TACI⁺IgA⁺Bregs was observed in IgAN patients. This may represent a beneficial compensatory response supported by APRIL; therefore, caution is warranted when using new anti-APRIL/BAFF therapies. The modulation of pathogenic and regulatory subpopulations in IgAN deserves further investigation to inform use of these B-cell directed therapies.

Acknowledgment

Supported by CureGN Pilot Grant Award and NephCure; Patients recrutied from CureGN registry