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Updated: Jul 15, 2025
In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
The predictive and prognostic value of peripheral blood antigen-specific memory B cells in phospholipase A2
Richard Zhu1, Hong Tang1, Lilian Howard2
1ImmunoWork, Monrovia, California, CA 91016-6353.
Background:
Phospholipase A2 receptor-associated membranous nephropathy (PLA2R-MN) is an anti-PLA2R antibody (PLA2R-Ab) mediated autoimmune kidney disease. Although antibody titer correlates closely with disease activity, whether it can provide longer-term predictions on disease course and progression is unclear. Rituximab, a B-cell depletion therapy, has become the first-line treatment option for PLA2R-MN; however, the response to Rituximab varies among patients.
Methods:
We developed a flow cytometry-based test that detects and quantifies PLA2R antigen-specific memory B cells (PLA2R-MBCs) in peripheral blood, the primary source for PLA2R-Ab production upon disease relapse. We applied the test to 159 blood samples collected from 28 patients with PLA2R-MN (at diagnosis, during and after immunosuppressive treatment, immunological remission, and relapse) to evaluate the relationship between circulating PLA2R-MBC levels and disease activity.
Results:
The level of PLA2R-MBCs in healthy controls (n=56) is less than or equal to 1.5% of the total MBC compartment. High circulating PLA2R-MBC levels were detected in two patients post-Rituximab despite achieving immunologic and proteinuric remission, as well as in two patients with negative serum autoantibody but increasing proteinuria. Elimination of these cells with Rituximab improved clinical outcomes. Moreover, five patients exhibited elevated PLA2R-MBC levels before disease relapse, followed by a rapid decline to baseline when relapse became clinically evident. COVID-19 vaccination or SARS-CoV-2 infection significantly affected the dynamics of circulating PLA2R-MBCs.
Conclusions:
This study suggests that monitoring PLA2R-MBC levels in patients with PLA2R-MN may help refine and individualize immunosuppressive therapy and predict disease course and progression. The technology and findings may also have broader applications in the clinical management of other autoimmune diseases.
Insights
Monitoring phospholipase A2 receptor-associated membranous nephropathy (PLA2R-MN) patients' PLA2R-memory B cells (PLA2R-MBCs) can predict disease relapse and treatment response. This approach may refine immunosuppressive therapy for better clinical outcomes in PLA2R-MN.
Area of Science:
- Immunology
- Nephrology
- Autoimmune Diseases
Background:
- Phospholipase A2 receptor-associated membranous nephropathy (PLA2R-MN) is an autoimmune kidney disease mediated by anti-PLA2R antibodies.
- While antibody titers correlate with disease activity, their predictive value for long-term disease course and progression remains unclear.
- Rituximab is a first-line treatment, but patient responses vary.
Approach:
- Developed a flow cytometry assay to detect and quantify PLA2R antigen-specific memory B cells (PLA2R-MBCs) in peripheral blood.
- Analyzed 159 blood samples from 28 PLA2R-MN patients at various disease stages (diagnosis, treatment, remission, relapse).
- Correlated circulating PLA2R-MBC levels with disease activity and clinical outcomes.
Key Points:
- Elevated PLA2R-MBCs were observed in patients post-Rituximab with remission and in those with proteinuria despite negative autoantibodies.
- PLA2R-MBC levels predicted impending disease relapse in five patients.
- COVID-19 vaccination or infection impacted PLA2R-MBC dynamics.
Conclusions:
- Monitoring PLA2R-MBCs can aid in personalizing immunosuppressive therapy for PLA2R-MN.
- PLA2R-MBC levels may predict disease course and progression.
- This methodology could be applicable to managing other autoimmune conditions.
