%0 Figure %A Cernoch, Marek %A Hruba, Petra %A Kollar, Marek %A Mrazova, Petra %A Stranavova, Lucia %A Lodererova, Alena %A Honsova, Eva %A Viklicky, Ondrej %D 2018 %T Image_1_Intrarenal Complement System Transcripts in Chronic Antibody-Mediated Rejection and Recurrent IgA Nephropathy in Kidney Transplantation.JPEG %U https://frontiersin.figshare.com/articles/figure/Image_1_Intrarenal_Complement_System_Transcripts_in_Chronic_Antibody-Mediated_Rejection_and_Recurrent_IgA_Nephropathy_in_Kidney_Transplantation_JPEG/7181423 %R 10.3389/fimmu.2018.02310.s001 %2 https://frontiersin.figshare.com/ndownloader/files/13214321 %K kidney transplantation %K complement %K chronic antibody-mediated rejection %K IgA nephropathy %K gene expression %X

Background: The complement system activation and regulation have been linked to post-transplant pathologies including chronic antibody mediated rejection (cAMR) and the recurrence of IgA nephropathy (ReIgAN) but distinct mechanisms remain to be elucidated.

Methods: In this retrospective single center study, the outcome of kidney transplantation was studied in 150 patients with late histological diagnosis to be either cAMR or ReIgAN, 14 stable kidney grafts at 3 months and finally 11 patients with native kidney IgAN nephropathy. To study a role of complement cascade and regulation in cAMR and ReIgAN, the RNA was extracted from available frozen kidney biopsy samples and using RT-qPCR transcripts of 11 target genes along with clinical data were determined and compared with stable grafts at 3 months protocol biopsies or IgAN native kidney nephropathy. Immunohistologically, CD46 (MCP), and C5 proteins were stained in biopsies.

Results: Interestingly, there were no differences in kidney graft survival between cAMR and ReIgAN since transplantation. cAMR was associated with significantly higher intragraft transcripts of C3, CD59, and C1-INH as compared to ReIgAN (p < 0.05). When compared to normal stable grafts, cAMR grafts exhibited higher C3, CD55, CD59, CFH, CFI, and C1-INH (p < 0.01). Moreover, ReIgAN was associated with the increase of CD46, CD55, CD59 (p < 0.01), and CFI (p < 0.05) transcripts compared with native kidney IgAN. Rapid progression of cAMR (failure at 2 years after biopsy) was observed in patients with lower intrarenal CD55 expression (AUC 0.77, 78.6% sensitivity, and 72.7 specificity). There was highly significant association of several complement intrarenal transcripts and the degree of CKD regardless the diagnosis; C3, CD55, CFH, CFI, and C1-INH expressions positively correlated with eGFR (for all p < 0.001). Neither the low mRNA transcripts nor the high mRNA transcripts biopsies were associated with distinct trend in MCP or C5 proteins staining.

Conclusions: The intrarenal complement system transcripts are upregulated in progressively deteriorated kidney allografts.

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