期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 125, 期 12, 页码 4655-4665出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI82267
关键词
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资金
- European FP7 Translink research program [603049]
- Societe d'Acceleration du Transfert de Technologies Quest Valorisation
- French National Agency of Research [ANR-11-JSV1-0008-01]
- Labex Transplantex
- Natural Science and Engineering Research Council of Canada [RGPIN/170241]
- Canadian Foundation for Innovation [22391]
- Region Pays de la Loire
- Agence Nationale de la Recherche (ANR) [ANR-11-JSV1-0008] Funding Source: Agence Nationale de la Recherche (ANR)
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 alpha-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 Donnees Informatisees et Validees 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.
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