1. DelCFHR3-1 influences graft survival in transplant patients with IgA nephropathy via complement-mediated cellular senescence
- Author
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Lucia Crispino, Emma Diletta Stea, Pasquale Gallo, Francesco Pesce, Paola Laghetti, Santiago Rodriguez de Cordoba, Loreto Gesualdo, Michele Battaglia, Francesca Cianciotta, Giuseppe Castellano, Giuseppe Lucarelli, Antonio Granata, Chiara Divella, Giovanni Stallone, Michele Rossini, Matteo Accetturo, Pesce, Francesco [0000-0002-2882-4226], Divella, Chiara [0000-0003-2717-3158], Accetturo, Mateo [0000-0002-5599-989X], Gallo, Pasquale [0000-0001-8914-2600], Rossini, Michele [0000-0002-5801-4136], Cianciotta, Francesca [0000-0003-3385-2691], Granata, Antonio [0000-0002-7026-3952], Lucarelli, Giuseppe [0000-0001-7807-1229], Rodríguez de Córdoba, Santiago [0000-0001-6401-1874], Stallone, Giovanni [0000-0002-2862-9017], Gesualdo, Loreto [0000-0002-4861-0911], Castellano, Giuseppe [0000-0002-0153-3795], Pesce, Francesco, Divella, Chiara, Accetturo, Mateo, Gallo, Pasquale, Rossini, Michele, Cianciotta, Francesca, Granata, Antonio, Lucarelli, Giuseppe, Rodríguez de Córdoba, Santiago, Stallone, Giovanni, Gesualdo, Loreto, and Castellano, Giuseppe
- Subjects
Senescence ,Kidney (allograft) function / dysfunction ,Complement factor I ,030230 surgery ,Kidney ,urologic and male genital diseases ,Nephropathy ,Glomerular biology and disease ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,medicine ,Genetics ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Cellular Senescence ,Transplantation ,medicine.diagnostic_test ,business.industry ,Graft Survival ,Glomerulonephritis, IGA ,medicine.disease ,Kidney Transplantation ,Complement system ,Complement biology ,Immunology ,Tubulointerstitial fibrosis ,Renal biopsy ,business ,Kidney disease - Abstract
8 p.-4 fig., IgA nephropathy (IgAN) is a frequent cause of chronic kidney disease (CKD) and pro-gressive renal impairment. A native renal biopsy diagnosis of IgAN is a predictor of graft loss, with a relative risk of 47% but it is difficult to predict graft survival and progressive allograft dysfunction in these patients. Deletion of complement factor H-related genes 1 and 3 (delCFHR3-1) has been associated with a decreased risk of developing IgAN on native kidneys, but the impact on the graft in IgAN-transplanted patients is unknown. We hypothesized that delCFHR3-1 is also associated with the processes that influence graft survival in transplant recipients with IgAN and tested whether cellular senescence is involved in mediating graft damage. We found that patients carrying two copies of CFHR1-3 had a worse outcome (P = .000321) and pre-sented increased FHR1 deposits at glomerular and tubulointerstitial level associated with higher expression of the senescence marker p16INK4a (P = .001) and tubulointer-stitial fibrosis (P = .005). Interestingly, FHR1 deposits were associated with increased complement activation as demonstrated by C5b-9 deposits. These data support both the role of FHR1 in mediating complement activation and tubular senescence, and suggest the possibility of genotyping delCFHR3-1 to predict graft survival in IgAN-transplanted patients.
- Published
- 2020