Circulating (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)) Plasmablasts: A Promising Cellular Biomarker for Immune...

Area of Science:

• Immunology
• Nephrology
• Autoimmune Diseases

Background:

• Membranous nephropathy (MN) is an autoimmune kidney disease primarily driven by anti-phospholipase A2 receptor 1 autoantibodies (PLA2R1 Ab).
• Assessing the efficacy of rituximab (RTX), an anti-CD20 monoclonal antibody, is crucial for improving clinical outcomes in MN patients.
• Plasmablasts are a potential biomarker for RTX response in autoimmune conditions.

Purpose of the Study:

• To evaluate the changes in plasmablasts, memory B cells, and naive B cells following RTX treatment in a patient with PLA2R1-related MN.
• To explore the utility of monitoring these B cell subsets as complementary tools for assessing RTX efficacy.

Main Methods:

• Fluorescence-activated cell sorter (FACS) analysis was used to quantify B cell populations (plasmablasts, memory B cells, naive B cells) in a single patient with PLA2R1-related MN.
• The analysis covered a 4-year follow-up period after RTX administration.
• Serum anti-PLA2R1 antibody levels were also monitored.

Main Results:

• RTX rapidly depleted CD19+ B cells, plasmablasts, and memory B cells by day 15.
• Plasmablasts and memory B cells reappeared earlier than naive B cells during follow-up.
• Despite a faster decrease than memory B cells, plasmablasts remained elevated compared to baseline, coinciding with a progressive increase in anti-PLA2R1 antibodies.

Conclusions:

• Enumerating circulating plasmablasts and memory B cells offers a valuable, complementary method to monitor immunological activity in anti-PLA2R1 Ab-related MN.
• These B cell subset analyses, alongside serum anti-PLA2R1 Ab levels, can help assess the efficacy of RTX-induced B cell depletion.