Kidney Week

Abstract: TH-PO0267

Detection of Anti-Mesangial IgA Antibody-Producing Memory B Cells in Patients with IgAN

Session Information

• Glomerular Diseases: Cell Biology
  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

• Kadota, Nozomi, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Nozomi Kadota, MD

• Nihei, Yoshihito, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Yoshihito Nihei, MD, PhD

• Ogiwara, Kei, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Kei Ogiwara, MD

• Aoki, Ryousuke, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Ryousuke Aoki, PhD

• Fukao, Yusuke, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Yusuke Fukao, MD

• Yamada, Koshi, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Koshi Yamada, MD, PhD

• Suzuki, Hitoshi, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Hitoshi Suzuki, MD, PhD

• Suzuki, Yusuke, Deparment of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan

Yusuke Suzuki, MD, PhD

Background

Recently, we identified β2-spectrin and CBX3 as target autoantigens on mesangial cells and demonstrated that these auto antibodies are involved in pathogenesis of IgA nephropathy. Furthermore, our previous data showed that recombinant antibodies established from tonsillar cells recognized β2-spectrin and harbored somatic hypermutations. We therefore hypothesized that the anti-mesangial auto antibodies are produced by germinal center–experienced B cells. In this study, we investigated whether anti-β2-spectrin IgA type auto antibody producing memory B cells (MBCs) are present in IgA nephropathy patients.

Methods

Among 46 IgA nephropathy patients who underwent tonsillectomy at Juntendo University Hospital between October 2024 and March 2026, we selected those with high titers of anti β2-spectrin IgA antibody in tonsillar mononuclear cell (TMNC) culture supernatants. IgA1+ MBCs (CD19+, IgM-, IgG-, CD27+, CD38-, IgA1+) were isolated as single cells into 384-well plates by flow cytometry and cultured. On day 12, the productions of the anti-β2-spectrin IgA antibody in the culture supernatants were assessed by ELISA.

Results

We first established a culture system in which IgA antibody production from a single MBC could be detected in the supernatant. Irradiated 40LB cells (BALB/c-3T3 fibroblasts transduced to express CD40 ligand and BAFF) were coated into ELISA plates, and individual MBCs from TMNCs were seeded onto irradiated 40LB cells. MBCs were co-cultured with these feeder cells, expanded with IL-2 and IL-21 until day 6, followed by secondary stimulation including APRIL and BAFF to induce differentiation into plasmablasts. In this system, approximately 60% of wells containing a single sorted MBC showed positive total IgA in the supernatant (5.3–500 ng/mL; mean 21.3 ng/mL). In patients with high anti-β2-spectrin IgA antibody titers in TMNC culture supernatants, ELISA of MBC supernatants contained a positive well of β2-spectrin (0.22–0.84%; mean 0.74%).

Conclusion

MBCs producing anti-β2-spectrin IgA auto antibody are present in IgA nephropathy patients. MBCs may be involved in the maintenance of anti-mesangial IgA auto antibodies.

Funding

• Commercial Support – Novartis