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Increased Late Graft Loss in Kidney Recipients With Serum Sickness Disease Following Anti-Thymocyte Globulin Induction: Relation With an Anti-Neu5Gc Response
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Edité par CCSD ; WILEY-BLACKWELL -
International audience. Anti-thymocyte globulins (ATG) are rabbit IgGs against human T cells widely used as induction treatment of kidney recipients. ATG can induce immune-complex diseases including Serum Sickness Diseases (SSD). Rabbit and human IgGs differ in the expression of the sialic acid Neu5Gc, and humans exhibit preexisting and produce elicited anti-Neu5Gc antibodies. We assessed here the role of SSD on long-term allograft outcome in a cohort of 889 first kidney graft recipients with ATG induction, grafted between 1985 and 1998 (n=86 with overt SSD and n=803 without SSD), and analyzed the immunization status of a subgroup of this population against some xeno-antigens. We show that SSD is associated with the risk of graft failure (death-censored, HR=1.72, p=0.022). Total anti-ATG, anti-Gal and anti-Neu5Gc IgG levels were analyzed in a case-control subgroup constituted of 14 SSD+ versus 42 SSD- patients matched for 5 variables (recipients age, date of graft, PRA class I/II positivity, HLA mismatches). No significant differences were found in preexisting antibodies of any type. SSD+ patients exhibited elevated titers of anti-ATG (p=0.001) and anti-Neu5Gc (p=0.054) between pre-graft and late post-graft samples. Anti-Neu5Gc IgGs were increased in late post-graft sera of SSD+ patients when compared to SSD- patients (p=0.020). Anti-Gal antibodies were not informative. Finally, late graft survival was associated with high anti-Neu5Gc IgG levels in late post-graft samples, independently of SSD status (p=0.025). In conclusion, we demonstrated that ATG-induced SSD is an independent risk factor of graft failure, and suggested that anti-Neu5Gc antibodies could have a role in allograft outcome following SSD.
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