Pozdzik Agnieszka, Beukinga Ingrid, Gu-Trantien Chunyan, Willard-Gallo Karen, Nortier Joëlle, Pradier Olivier
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.
Department of Hematology, Cliniques Universitaires de Bruxelles (CUB), Erasme Hospital, 1070 Brussels, Belgium.
Mediators Inflamm. 2016;2016:7651024. doi: 10.1155/2016/7651024. Epub 2016 Jul 14.
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.
膜性肾病（MN）是一种主要由抗磷脂酶A2受体1自身抗体（PLA2R1 Ab）介导的肾脏特异性自身免疫性疾病。仍需要对嵌合抗CD20单克隆抗体利妥昔单抗（RTX）的疗效进行充分评估，以改善MN患者的临床结局。我们通过荧光激活细胞分选分析评估了浆母细胞（CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)）的变化，浆母细胞是其他自身免疫性疾病中RTX反应的一个有用生物标志物，以及记忆性（CD3(-)CD19(+)CD20(+)IgD(-)CD27(+)CD38(-)）和初始（CD3(-)CD19(+)CD20(+)IgD(+)CD27(-)CD38(low)）B细胞，该分析是在一名PLA2R1相关MN患者接受RTX治疗后的4年随访期间进行的。RTX在第15天就导致CD19(+) B细胞、浆母细胞和记忆性B细胞完全消失。尽管出现严重的CD19(+)淋巴细胞减少，但浆母细胞和记忆性B细胞在初始B细胞之前就早早重新出现（分别在第45天、90天和120天）。在随访期间，浆母细胞比记忆性B细胞下降得更快，但与RTX治疗第0天相比仍保持升高。与此同时，抗PLA2R1 Ab逐渐增加。我们的单病例报告表明，除了监测血清抗PLA2R1 Ab水平外，循环浆母细胞和记忆性B细胞的计数是评估抗PLA2R1 Ab相关MN中RTX诱导的B细胞耗竭的免疫活性和疗效的一种有吸引力的补充工具。
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