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Circulating (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)) Plasmablasts: A Promising Cellular Biomarker for Immune
Agnieszka Pozdzik1, Ingrid Beukinga2, Chunyan Gu-Trantien3
1Department of Nephrology, Dialysis and Renal Transplantation, Cliniques Universitaires de Bruxelles (CUB), Erasme Hospital, 1070 Brussels, Belgium; Unit of Experimental Nephrology, Department of Biochemistry, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
Abstract:
Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3(-)CD19(+)CD20(+)IgD(-)CD27(+)CD38(-)) and naive (CD3(-)CD19(+)CD20(+)IgD(+)CD27(-)CD38(low)) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19(+) B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19(+) lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN.
Insights
Rituximab (RTX) treatment for membranous nephropathy (MN) depletes B cells, including plasmablasts and memory B cells. Monitoring these cells alongside anti-PLA2R1 antibody levels can assess RTX efficacy in this kidney disease.
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.
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