title: Rabbit antithymocyte globulin-induced serum sickness disease and human kidney graft survival.
abstract: BACKGROUND
  Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and α-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment.
  
  
  METHODS
  We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation.
  
  
  RESULTS
  SSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients.
  
  
  CONCLUSIONS
  In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients.
  
  
  BACKGROUND
  This study was funded by Société d'Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Couvrat-Desvergnes
authors.forename: Apolline
authors.initials: A
authors.lastname: Salama
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Le Berre
authors.forename: Gwénaëlle
authors.initials: G
authors.lastname: Evanno
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
authors.forename: Petra
authors.initials: P
authors.lastname: Hruba
authors.forename: Pavel
authors.initials: P
authors.lastname: Vesely
authors.forename: Pierrick
authors.initials: P
authors.lastname: Guerif
authors.forename: Thomas
authors.initials: T
authors.lastname: Dejoie
authors.forename: Juliette
authors.initials: J
authors.lastname: Rousse
authors.forename: Arnaud
authors.initials: A
authors.lastname: Nicot
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bach
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ang
authors.forename: Yohann
authors.initials: Y
authors.lastname: Foucher
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Castagnet
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.forename: Jean
authors.initials: J
authors.lastname: Harb
authors.forename: Hélène
authors.initials: H
authors.lastname: Perreault
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
authors.forename: Marine
authors.initials: M
authors.lastname: Lorent
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000097:blood; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D012713:Serum Sickness / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D012794:Sialic Acids / Q000097:blood
chemical_list: D000961:Antilymphocyte Serum; D007518:Isoantibodies; C078888:N-(O-acetyl)glycoloylneuraminic acid; D012794:Sialic Acids