title: A non-allogeneic stimulus triggers the production of de novo HLA antibodies in healthy adults.
abstract: BACKGROUND
  Transplant recipients develop antibodies against a wide array of HLA specificities, and not only against the antigens to which they have been exposed. The aim of the present study was to establish if HLA-unrelated immune stimulation is capable of triggering the production of HLA antibodies.
  
  
  METHODS
  We determined the presence of HLA antibodies in 20 healthy adults before and after the administration of an immune stimulus (hepatitis B vaccine plus tuberculin skin test). HLA antibodies were assessed with a flow-cytometry based system.
  
  
  RESULTS
  At baseline, HBsAg antibodies were detected in protective titers in 75% of the subjects; HLA antibodies were negative in all but one. One week after the antigenic stimulus, HBsAg antibody titers increased significantly, without any detectable changes in HLA antibodies. Surprisingly, HLA antibodies developed in 8 participants one month after the application of the stimulus. One additional subject developed HLA antibodies one month later. Therefore 9/20 subjects became PRA positive during the observation period. Antibody specificities were identified by single antigen assay. The alloantibody response elicited by the immune stimulus was not consistent with memory cell stimulation.
  
  
  CONCLUSIONS
  The findings of this study demonstrate that a non-HLA antigenic stimulus is capable of eliciting the development of HLA antibodies in healthy adults.
authors.affiliation: Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14000, Mexico City, Mexico.
authors.forename: Josefina
authors.initials: J
authors.lastname: Alberú
authors.forename: Luis E
authors.initials: LE
authors.lastname: Morales-Buenrostro
authors.forename: Claudia
authors.initials: C
authors.lastname: de Leo
authors.forename: María Inés
authors.initials: MI
authors.lastname: Vargas-Rojas
authors.forename: Lluvia A
authors.initials: LA
authors.lastname: Marino-Vázquez
authors.forename: José C
authors.initials: JC
authors.lastname: Crispín
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006680:HLA Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014181:Transplantation Immunology; D014374:Tuberculin Test
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D017325:Hepatitis B Vaccines; D007518:Isoantibodies