Kidney Week

Abstract: FR-OR085

Proliferation and Changes in Cellular Signatures in Memory B Cells from Lupus Nephritis Patients Receiving Mycophenolate or Azathioprine Maintenance

Session Information

• Lupus and Then Some
  November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Yap, Desmond Y.H., Queen Mary Hospital, Hong Kong, HONG KONG, China

Desmond Y.H. Yap, MD, MBBS



Dr. Desmond YAP is currently Clinical Associate Professor and Honorary Consultant, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong. His research interests include the immunopathogenesis and the use of immunosuppressive treatments in glomerular diseases, with special focus on lupus nephritis. He received the Hong Kong Society of Nephrology Young Investigator Award in 2009 for his investigation on serum immunoglobulin binding activity to human mesangial cells in lupus nephritis. He obtained his Doctor of Medicine (MD) at the University of Hong Kong in 2014, and was awarded the Li Shu Pui Clinical Fellowship (2014-2015) to work as research fellow at the Fiebiger-Nikolaus Centre, Friedrich-Alexander University, Germany. Dr. Yap later also obtained his Doctor of Philosophy (PhD) at the University of Hong Kong in 2019. He served as the Honorary Secretary for the Asian Lupus Nephritis Network (ALNN) and also for the Hong Kong Society for Histocompatibility and Immunogenetics (HKSHI). Dr. Yap is also a Councilor of the Hong Kong Society of Nephrology (HKSN) and the Hong Kong Society of Transplantation. Dr. Yap published over 90 internationally peer-reviewed articles and currently serves as Subject Editor for Nephrology (Carlton). He is also a regular reviewer of Nephrology Dialysis Transplantation, International Journal of Rheumatic Diseases and Peritoneal Dialysis International

• Lee, Paul, The University of Hong Kong, Hong Kong, China

Paul Lee,

• Tam, Cheryl, The University of Hong Kong, Hong Kong, China

Cheryl Tam,

• Yam, Irene, The University of Hong Kong, Hong Kong, China

Irene Yam,

• Yung, Susan, The University of Hong Kong, Hong Kong, China

Susan Yung,

• Chan, Daniel Tak Mao, Queen Mary Hospital, Hong Kong, HONG KONG, China

Daniel Tak Mao Chan,

Background

Mycophenolate mofetil (MMF) and azathioprine (AZA) are standard maintenance treatments for lupus nephritis (LN), and recent data suggested lower risk of relapse with MMF maintenance. Memory B cells have been implicated in LN relapse, and miRNA148a, BACH1, BACH2 and PAX5 can regulate memory B cell homeostasis. The effects of MMF and AZA treatment on these memory B cell signatures remain unclear.

Methods

Memory B cells were isolated from clinically stable LN patients receiving low-dose corticosteroid and MMF (n=10) or AZA (n=9) maintenance, and the cell proliferation and intracellular miRNA148a, BACH1, BACH2 and PAX5 expressions on Day 3 after ex vivo stimulation were compared.

Results

MMF group showed lower memory B cell proliferation on Day 3 (8.5±1.2%, compared with 20.3±2.0% in AZA group, p<0.001) (Figure 1, A). MMF group also showed lower miRNA148a expression (10-fold decrease compared to health controls (HC), vs. 2-fold decrease in AZA group, p<0.001) (Figure 1, B), but higher BACH1, BACH and PAX5 expression in memory B cells (8.2±0.8, 7.2±1.8, and 7.6±1.1 fold increase compared to HC respectively, vs. 4.0±0.7, 2.9±0.6, and 3.4±0.4 fold increase in the AZA group, p<0.001, MMF vs. AZA) (Figure 1, C).

Conclusion

LN patients receiving MMF maintenance showed reduced memory B cell proliferation and a distinct cellular signature, which may account for the lower risk of relapse observed clinically.