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- Title
MICA Mutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation.
- Authors
Tonnerre, Pierre; Gérard, Nathalie; Gavlovsky, Pierre-Jean; Mazalrey, Simon; Hourmant, Maryvonne; Cheneau, Mary-Luce; Cesbron-Gautier, Anne; Renaudin, Karine; Bressollette-Bodin, Céline; Charreau, Béatrice
- Abstract
<bold>Background: </bold>BK polyomavirus (BKPyV) frequently reactivates in kidney transplant recipients during immunosuppressive therapy and triggers BKPyV-associated nephropathy and graft rejection. Determining effective risk factors for BKPyV reactivation is required to achieve efficient prevention.<bold>Methods: </bold>This study investigated the role of major histocompatibility complex (MHC) class I-related chain A (MICA) in BKPyV reactivation in a cohort of 144 transplant donor/recipient pairs, including recipients with no reactivation (controllers) and those with mild (virurics) or severe (viremics) BKPyV reactivation after graft receipt.<bold>Results: </bold>We show that, in the kidney, MICA is predominantly expressed in tubule epithelial cells, the natural targets of BKPyV, questioning a role for MICA in the immune control of BKPyV infection. Focusing on MICA genotype, we found a lower incidence of BKPyV reactivation in recipients of a renal graft from a donor carrying the MICA A5.1 mutant, which encodes a truncated nonconventional MICA. We established that a mismatch for MICA A5.1 between transplant donor and recipient is critical for BKPyV reactivation and BKPyV-associated nephropathy. Functionally, we found that a low prevalence of BKPyV reactivation was associated with elevated anti-MICA sensitization and reduced plasma level of soluble MICA in recipients, 2 potential effector mechanisms.<bold>Discussions: </bold>These findings identify the MHC-related MICA as an immunogenetic factor that may functionally influence anti-BKPyV immune responses and infection outcomes.
- Subjects
KIDNEY diseases; KIDNEY transplantation; IMMUNOSUPPRESSIVE agents; HISTOCOMPATIBILITY; EPITHELIAL cells; DISEASE prevalence
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 5, p807
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw168