کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8739547 | 1592260 | 2018 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Autoantibodies against podocytic UCHL1 are associated with idiopathic nephrotic syndrome relapses and induce proteinuria in mice
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Idiopathic steroid sensitive nephrotic syndrome (INS), the most frequent childhood nephropathy, is thought to be mediated by a circulating soluble factor that reversibly affects the renal protein sieving. The efficiency of rituximab therapy recently highlighted the involvement of B cells. Here we studied the involvement of a specific immunoglobulin G (IgG) in the disease. After plasma fractionation by size exclusion chromatography, a detachment of cultured podocyte was observed with one IgG-containing fraction from 47% patients in relapse, 9% of patients in remission and 0% of controls. Podocyte protein lysates were immunoprecipitated by IgG from those plasma fractions identifying a list of 41 podocyte proteins after proteomic analysis. Five podocyte targets were selected on statistical and biological criteria. Specific antibodies were tested and only anti-Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) IgG led to podocyte detachment. UCHL1 was mainly found inside the podocyte but also weakly expressed on podocyte cell surface. Incubation of either anti-UCHL1 IgG or plasma fractions with recombinant UCHL1 prevented podocyte detachment. Plasma levels of anti-UCHL1 IgG were significantly increased in relapsing INS patients compared to patients in remission and controls. Proteinuria correlated with anti-UCHL1 IgG level at various stages of the disease. Purified patient anti-UCHL1 antibodies induced proteinuria and podocyte foot effacement in mice. Altogether, these results identified UCHL1 as a target podocyte protein of autoantibodies in a set of relapsing patients and support a causative role of anti-UCHL1 autoantibodies in the development of INS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Autoimmunity - Volume 89, May 2018, Pages 149-161
Journal: Journal of Autoimmunity - Volume 89, May 2018, Pages 149-161
نویسندگان
Agnès Jamin, Laureline Berthelot, Anne Couderc, Jonathan M. Chemouny, Erwan Boedec, Laurène Dehoux, Lilia Abbad, Claire Dossier, Eric Daugas, Renato C. Monteiro, Georges Deschênes,