Delville Marianne, Baye Emilie, Durrbach Antoine, Audard Vincent, Kofman Tomek, Braun Laura, Olagne Jérôme, Nguyen Clément, Deschênes Georges, Moulin Bruno, Delahousse Michel, Kesler-Roussey Gwenaëlle, Beaudreuil Séverine, Martinez Frank, Rabant Marion, Grimbert Philippe, Gallazzini Morgan, Terzi Fabiola, Legendre Christophe, Canaud Guillaume
Université Paris Descartes, Sorbonne Paris Cité, Service de Biothérapie.
Institut National de la Santé et de la Recherche Médicale U1151, Institut Necker Enfants Malades.
J Am Soc Nephrol. 2016 Aug;27(8):2520-7. doi: 10.1681/ASN.2015091002. Epub 2015 Dec 23.
FSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7-1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7-1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7-1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7-1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7-1 blockade did not induce FSGS remission after transplant in our study.
局灶节段性肾小球硬化症(FSGS)是一种常见的肾小球疾病,肾移植后复发倾向较高。FSGS的病理生理学尚不清楚,但足细胞似乎是导致细胞骨架重组和蛋白尿的一种或几种循环因子的作用靶点。对足细胞的研究已确定B7-1是足细胞生物学中的一个重要因子,也是肾脏疾病的一个新治疗靶点。事实上,在4例移植后复发性FSGS患者中,使用B7-1阻滞剂阿巴西普治疗与蛋白尿缓解相关。在此,我们前瞻性地使用阿巴西普或亲和力更高的B7-1阻滞剂贝拉西普治疗了9例移植后复发性FSGS患者,但未诱导蛋白尿缓解。此外,我们在这些或其他肾移植活检标本的足细胞或天然肾活检标本的足细胞中,通过免疫荧光未检测到B7-1表达。总之,在我们的研究中,B7-1阻断并未诱导移植后FSGS缓解。