AUTHOR=Cernoch Marek , Hruba Petra , Kollar Marek , Mrazova Petra , Stranavova Lucia , Lodererova Alena , Honsova Eva , Viklicky Ondrej 

TITLE=Intrarenal Complement System Transcripts in Chronic Antibody-Mediated Rejection and Recurrent IgA Nephropathy in Kidney Transplantation

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02310

DOI=10.3389/fimmu.2018.02310

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Interestingly, there were no differences in kidney graft survival between cAMR and ReIgAN since transplantation. cAMR was associated with significantly higher intragraft transcripts of <italic>C3, CD59</italic>, and <italic>C1-INH</italic> as compared to ReIgAN (<italic>p</italic> &lt; 0.05). When compared to normal stable grafts, cAMR grafts exhibited higher <italic>C3, CD55, CD59, CFH, CFI</italic>, and <italic>C1-INH</italic> (<italic>p</italic> &lt; 0.01). Moreover, ReIgAN was associated with the increase of <italic>CD46, CD55, CD59</italic> (<italic>p</italic> &lt; 0.01), and <italic>CFI</italic> (<italic>p</italic> &lt; 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; <italic>C3, CD55, CFH, CFI</italic>, and <italic>C1-INH</italic> expressions positively correlated with eGFR (for all <italic>p</italic> &lt; 0.001). Neither the low mRNA transcripts nor the high mRNA transcripts biopsies were associated with distinct trend in MCP or C5 proteins staining.</p><p><bold>Conclusions:</bold> The intrarenal complement system transcripts are upregulated in progressively deteriorated kidney allografts.</p>