Abstract: TH-PO1006
BAFF-Dependent IgA Production Does Not Play a Pivotal Role in the Pathogenesis of Murine IgA Nephropathy
Session Information
- Glomerular Diseases: Minimal Change Disease, FSGS, IgAN
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Kim, Jin sug, Kyung Hee University School of Medicine, Seoul, Korea (the Republic of)
- Suzuki, Hitoshi, Juntendo University Faculty of Medicine, Tokyo, Japan
- Kano, Toshiki, Juntendo University Faculty of Medicine, Tokyo, Japan
- Fukao, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
- Nakayama, Maiko, Juntendo University Faculty of Medicine, Tokyo, Japan
- Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although our understanding of this disease have improved by remarkable progress, its pathogenesis has not yet clearly understood. Recent studies suggested B cell activating factor belonging to the TNF family (BAFF), which participates in the activation of B cells and class switch of IgA, as a potential disease marker of IgAN. However, the role of BAFF in the development and progression of IgAN remains unclear. In this study, we investigated the pathological role of BAFF in IgAN using a grouped ddY mice which is the spontaneous murine model of IgAN.
Methods
Mice with IgAN designated grouped ddY were treated with PBS or anti-BAFF monoclonal antibody (anti-BAFF Ab) by intraperitoneal injection every three days for four weeks. We measured the levels of urinary albumin, serum immunoglobulins (IgA, IgG, and IgM), and serum IgA-IgG immune complex at the beginning and end of the treatment. The levels of serum aberrantly glycosylated IgA were also measured using biotinylated Ricinus communis agglutinin-I (RCA-I) and Sambucus nigra bark lectin (SNA). We further assessed glomerular depositions of IgA and C3 by immunofluorescence staining, and analyzed changes of B cell population in spleen and bone marrow using flow cytometric analysis.
Results
Anti-BAFF Ab treatment significantly decreased serum levels of IgA, IgG, and IgM as compared with PBS treatment in the murine IgAN model (p < 0.001, p = 0.003, and p = 0.002, respectively). However, it did not affect urinary albumin excretion, serum levels of IgA-IgG immune complex, and serum levels of aberrantly glycosylated IgA. Glomerular depositions of IgA and C3 as well as B cell population in spleen and bone marrow were also not affected by anti-BAFF Ab treatment.
Conclusion
Anti-BAFF Ab treatment was effective to inhibit the production of immunoglobulins, but not nephritogenic IgA in murine IgAN model. Our results suggest that BAFF-dependent IgA production may not play a pivotal role in the pathogenesis of IgAN.