title: Harmful effect of preformed anti-MICA antibodies on renal allograft evolution in early posttransplantation period.
abstract: BACKGROUND
  Pretransplantation anti-major histocompatibility complex class I chain-related molecule A (MICA) sensitization is an uncommon event and its role on kidney graft evolution is not completely defined.
  
  
  METHODS
  A retrospective study of patients transplanted between 2005 and 2011 in our center (n=727) was performed. Recipients were classified in four groups, according either to multiplexed flow cytometry-recorded anti-human leukocyte antigen (HLA) and anti-MICA antibodies or to percent panel-reactive antibody (PRA; by complement-dependent cytotoxicity) and anti-MICA antibodies.
  
  
  RESULTS
  In the total cohort, 52 (7.15%) patients had preformed anti-MICA antibodies, and these were not related with anti-HLA, previous transplantations, or recipient female sex (potential pregnancies). Kaplan-Meier curves showed global allograft survival differences (P=0.042) mostly due to pronounced decrease in PRA+MICA+ group early after transplantation. Biopsy-proven allograft rejection rate increased after month 12 in PRA+MICA- group and was higher early after transplantation in PRA+MICA+ group (P=0.033). In paired comparisons, rejection incidence was superior in PRA+MICA- versus PRA-MICA- patients (17% vs. 7%; P=0.007) at 24 months, confirming the widely reported deleterious effect of PRA+ status, but at 3 months rejection was higher in PRA+MICA+ versus PRA-MICA- patients (14% vs. 2%; P=0.009). Among patients categorized according anti-HLA and anti-MICA antibodies, the most striking difference in rejection was observed at 3 months (8% in HLA-MICA+ vs. 2% in HLA-MICA- patients; P=0.032). In the multivariate analysis, HLA-MICA+ status at 3 months independently conferred the highest risk for rejection (odds ratio, 5.07; P=0.049).
  
  
  CONCLUSIONS
  Pretransplantation sensitization against MICA and HLA are independent events. Preformed anti-MICA antibodies independently increase risk for kidney rejection and enhance the deleterious effect of PRA+ status early after transplantation.
authors.affiliation: Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain. esanchezz@salud.madrid.org
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez-Zapardiel
authors.forename: María J
authors.initials: MJ
authors.lastname: Castro-Panete
authors.forename: Marcela
authors.initials: M
authors.lastname: Castillo-Rama
authors.forename: Pablo
authors.initials: P
authors.lastname: Morales
authors.forename: David
authors.initials: D
authors.lastname: Lora-Pablos
authors.forename: Diana
authors.initials: D
authors.lastname: Valero-Hervás
authors.forename: Raquel
authors.initials: R
authors.lastname: Ruiz-García
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Apaza
authors.forename: Paloma
authors.initials: P
authors.lastname: Talayero
authors.forename: Amado
authors.initials: A
authors.lastname: Andrés
authors.forename: José M
authors.initials: JM
authors.lastname: Morales
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D014850:Waiting Lists; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; C099187:MHC class I-related chain A