title: Circulating (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)) Plasmablasts: A Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related Membranous Nephropathy?
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.
authors: Department 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.
authors: Agnieszka
authors: 0000-0002-4317-1446
authors: A
authors: Pozdzik
authors: Department of Hematology, Cliniques Universitaires de Bruxelles (CUB), Erasme Hospital, 1070 Brussels, Belgium.
authors: Ingrid
authors: I
authors: Beukinga
authors: Unit of Molecular Immunology, Institute Jules Bordet, Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium.
authors: Chunyan
authors: 0000-0003-2891-590X
authors: C
authors: Gu-Trantien
authors: Unit of Molecular Immunology, Institute Jules Bordet, Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium.
authors: Karen
authors: K
authors: Willard-Gallo
authors: Department 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.
authors: Joëlle
authors: J
authors: Nortier
authors: Department of Hematology, Cliniques Universitaires de Bruxelles (CUB), Erasme Hospital, 1070 Brussels, Belgium.
authors: Olivier
authors: O
authors: Pradier
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology* / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D015433:Glomerulonephritis, Membranous / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism*; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D015415:Biomarkers; D017252:CD3 Complex; D007072:Immunoglobulin D; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051997:ADP-ribosyl Cyclase 1