title: MICA Mutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings identify the MHC-related MICA as an immunogenetic factor that may functionally influence anti-BKPyV immune responses and infection outcomes.
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, LabEx IGO and IHU-CESTI CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN LUNAM, Université de Nantes, Faculté de Médecine.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tonnerre
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, LabEx IGO and IHU-CESTI CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN LUNAM, Université de Nantes, Faculté de Médecine.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gérard
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, LabEx IGO and IHU-CESTI CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN LUNAM, Université de Nantes, Faculté de Médecine.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Gavlovsky
authors.affiliation: EA4271, Université de Nantes, UFR Pharmacie.
authors.forename: Simon
authors.initials: S
authors.lastname: Mazalrey
authors.affiliation: CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN LUNAM, Université de Nantes, Faculté de Médecine.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Hourmant
authors.affiliation: Laboratoire HLA, Etablissement Français du sang, LabEx Transplantex.
authors.forename: Mary-Luce
authors.initials: ML
authors.lastname: Cheneau
authors.affiliation: Laboratoire HLA, Etablissement Français du sang, LabEx Transplantex.
authors.forename: Anne
authors.initials: A
authors.lastname: Cesbron-Gautier
authors.affiliation: Laboratoire d'Anatomopathologie, CHU de Nantes, Université de Nantes, Faculté de Médecine.
authors.forename: Karine
authors.initials: K
authors.lastname: Renaudin
authors.affiliation: EA4271, Université de Nantes, UFR Pharmacie Laboratoire de Virologie, CHU de Nantes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bressollette-Bodin
authors.affiliation: INSERM, UMR1064, LabEx Transplantex, LabEx IGO and IHU-CESTI CHU Nantes, Institut de Transplantation et de Recherche en Transplantation-Urologie-Néphrologie, ITUN LUNAM, Université de Nantes, Faculté de Médecine.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001739:BK Virus / Q000276:immunology* / Q000502:physiology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009393:Nephritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D027601:Polyomavirus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D012189:Retrospective Studies; D014775:Virus Activation
chemical_list: D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C099187:MHC class I-related chain A
keywords: BK polyomavirus; MICA A5.1 mutation; MICA polymorphism; innate immunity; kidney transplantation