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. CONCLUSION: 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. FUNDING: 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.
RCT Entities:
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 acidNeu5Gc 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. CONCLUSION: 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. FUNDING: 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: Andrea Bacigalupo; Teresa Lamparelli; Giovanni Barisione; Paolo Bruzzi; Stefano Guidi; Paolo Emilio Alessandrino; Paolo di Bartolomeo; Rosi Oneto; Barbara Bruno; Nicoletta Sacchi; Maria Teresa van Lint; Alberto Bosi Journal: Biol Blood Marrow Transplant Date: 2006-05 Impact factor: 5.742
Authors: Annie N Samraj; Oliver M T Pearce; Heinz Läubli; Alyssa N Crittenden; Anne K Bergfeld; Kalyan Banda; Christopher J Gregg; Andrea E Bingman; Patrick Secrest; Sandra L Diaz; Nissi M Varki; Ajit Varki Journal: Proc Natl Acad Sci U S A Date: 2014-12-29 Impact factor: 11.205
Authors: A O Gaber; M R First; R J Tesi; R S Gaston; R Mendez; L L Mulloy; J A Light; L W Gaber; E Squiers; R J Taylor; J F Neylan; R W Steiner; S Knechtle; D J Norman; F Shihab; G Basadonna; D C Brennan; E E Hodge; B D Kahan; L Kahan; S Steinberg; E S Woodle; L Chan; J M Ham; T J Schroeder Journal: Transplantation Date: 1998-07-15 Impact factor: 4.939
Authors: Sandra L Diaz; Vered Padler-Karavani; Darius Ghaderi; Nancy Hurtado-Ziola; Hai Yu; Xi Chen; Els C M Brinkman-Van der Linden; Ajit Varki; Nissi M Varki Journal: PLoS One Date: 2009-01-21 Impact factor: 3.240
Authors: Ron Amon; Shani Leviatan Ben-Arye; Limor Engler; Hai Yu; Noha Lim; Ludmilla Le Berre; Kristina M Harris; Mario R Ehlers; Stephen E Gitelman; Xi Chen; Jean-Paul Soulillou; Vered Padler-Karavani Journal: Oncotarget Date: 2017-12-11
Authors: Hoa Le Mai; Michèle Treilhaud; Shani Leviatan Ben-Arye; Hai Yu; Hélène Perreault; Evelyn Ang; Katy Trébern-Launay; Julie Laurent; Stéphanie Malard-Castagnet; Anne Cesbron; Thi Van Ha Nguyen; Sophie Brouard; Lionel Rostaing; Pauline Houssel-Debry; Christophe Legendre; Sophie Girerd; Michèle Kessler; Emmanuel Morelon; Antoine Sicard; Valérie Garrigue; Georges Karam; Xi Chen; Magali Giral; Vered Padler-Karavani; Jean Paul Soulillou Journal: Transplant Direct Date: 2018-03-20