Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis.
Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis.
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DOI：
10.1007/s00467-014-2957-6
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发表时间：
2015-03
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影响因子：
--
通讯作者：
Johnson RJ
中科院分区：
文献类型：
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作者：
Garin EH;Reiser J;Cara-Fuentes G;Wei C;Matar D;Wang H;Alachkar N;Johnson RJ
微小病变(MCD)复发与足细胞CD80表达增加和尿CD80排泄增加有关，而局灶性节段性肾小球硬化(FSGS)则表现为CD80表达轻度或缺失，尿CD80排泄正常。1例MCD患者、1例原发FSGS患者和3例移植后复发的FSGS患者接受了CD80封闭抗体(abatacept或belatacept)治疗。采用双抗体夹心法测定尿CD80和CTLA-4水平。肾小球CD80染色。停药后，MCD患者的尿CD80变得无法检测到，伴随着蛋白尿的短暂消失。相反，在一名初发FSGS患者和两名复发性FSGS患者中，尽管存在轻微的CD80肾小球表达但尿液CD80排泄正常，但经停药或培拉泰普治疗后，蛋白尿保持不变。1例移植后复发的FSGS患者术后即刻尿CD80排泄量升高，在停药前自发性下降。停药后，他的蛋白尿在5天内没有变化，尽管尿CD80排泄正常。这些观察结果与足细胞CD80在MCD蛋白尿发生中的作用一致。相反，CD80在复发的FSGS中可能不起作用，因为术后尿CD80只是一过性升高，而尿CD80的正常化并不能导致蛋白尿的消失。
Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 were measured by ELISA. Glomeruli were stained for CD80. After abatacept, urinary CD80 became undetectable with concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in one patient with primary FSGS and in two recurrent FSGS subjects despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. One patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before abatacept. After Abatacept, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since urinary CD80 is only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.