Of note, rabbit IgG (as well as horse IgGs) did not display Neu5Ac (Supplemental Physique 5)

Of note, rabbit IgG (as well as horse IgGs) did not display Neu5Ac (Supplemental Physique 5). using ELISA assays on sera before and after transplantation. RESULTS. SSD was significantly associated with long-term graft loss (>10 Cariporide years, = 0.02). Moreover, SSD+ patients exhibited significantly elevated titers of anti-ATG (= 0.043) and anti-Neu5Gc (= 0.007) IgGs in late post-graft samples compared with SSDC recipients. CONCLUSION. In conclusion, our data indicate that SSD is usually 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 Socit dAcclration 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. Introduction Polyclonal anti-human T lymphocyte IgGs (antithymocyte globulins [ATGs]) from numerous animal sources have been used since the CCL4 very beginning of allotransplantation (1, 2). ATGs are administered either immediately following medical procedures (refereed to as induction treatment) to decrease early rejection (3) or as treatment for acute rejection (4), particularly in steroid-resistant cases (5). Despite being associated with a higher incidence of bacterial and viral opportunistic infections and their related complications (3, 6), ATGs are being increasingly used as induction treatment in patients exhibiting high immunological risks (3, 7, 8). ATGs are also used in other T cellCmediated diseases, such as malignancies, graft-versus-host disease (9), and aplastic anemia (10). ATG treatment, which involves a polyclonal and foreign antiCT cell agent, has been associated with severe side effects, such as cytokine release storm (11), or immune complex disease symptoms, ranging from fever and skin rashes to serum sickness disease (SSD) (12). SSD occurs in almost all cases in which ATG is not associated with immunosuppressive drugs (13). Early biochemical characterization of the major antigenic determinants of ATG stressed the role of heterophilic epitopes and, particularly, of the Neu5Gc antigen, coined as the serum sickness antigen (12, 14C16). Humans cannot synthesize the sialic acid Neu5Gc (glycolyl form of neuraminic acid) from your acetylated form, Neu5Ac, following the mutation of the cytidine monophosphate-= 86) and SSDC patients (= 803) at baseline Open in a separate window Differences between SSD+ and SSDC patients in cohort A Among the 889 patients, 86 (9.7%) exhibited a SSD within the first month following induction onset. They were more youthful (= 0.02) and received allografts from younger donors Cariporide (= 0.02) than SSDC patients (Table 1). Multivariate analysis identified three variables significantly associated with SSD occurrence status: young donor, recipient ages, and transplantation before 1990 (Table 2). Patients from your SSD+ group exhibited significantly more biopsy-proven acute rejection episodes (AREs, Cariporide = 39, 45.3%) compared with SSDC patients (= 236, 29.4%, = 0.003). AREs occurred after SSD onset with no time overlap, at a median of 4.7 months after transplant, and only one patient experienced an ARE diagnosed within the first month. Table 2 Clinical features associated with the occurrence of SSD following ATG induction treatment: multivariate logistic regression model (= 889) Open in a separate window Relationship between SSD occurrence and graft survival in cohort A Multivariate analysis showed that SSD occurrence was significantly associated with late graft failure (>10 years), with a 1.72-fold relative risk of late graft failure (death censored) compared with SSDC patients (95% CI = 1.08C2.72), = 0.02). Death-censored graft survival is shown in Physique 2, and survival of these patients is shown in Table 3. At 15 years posttransplantation, 352 recipients (315 SSDC and 37 SSD+) of the initial global sample returned to dialysis, 169 died (153 SSDC and 16 SSD+), and 272 remained alive with a functioning kidney (246.