engleski

Association of Kidney Graft Loss With Posttransplant Presence of Strong HLA Antibodies Detected by Luminex Single Antigen Testing

Background. It is a matter of debate whether alloantibodies should be monitored in all kidney transplant recipients in order to combat antibody-mediated graft loss. Methods. In the Collaborative Transplant Study Serum Project, there were 64 patients with graft loss on whom a posttransplant serum 1-year before failure was available, as well as recipient and donor DNA for complete HLA typing, including HLA A, B, C, DRB1/3/4/5, DQA1, DQB1, DPA1, or DPB1 antigens, which allowed the precise definition of donor-specific antibodies (DSA). We compared the incidence of Luminex Single Antigen (SA)-detected DSA and non-DSA antibodies in these patients with graft failure and in matched controls with functioning grafts (non-rejectors). Positivity cut-offs at 500, 1000, 2000, 3000, and 5000 MFI (mean fluorescence intensity) were analyzed systematically. Results. At cut-off 500, as many as 95% of patients with graft loss and 94% of patients without graft loss showed evidence of Luminex-detected HLA antibodies. The incidence of DSA in patients with and without graft failure was with 44% and 36%, respectively, not significantly different between the two groups. However, with increasing cut-offs the difference between the two patient groups became more pronounced. When MFI of 5, 000 was used as cut-off for Luminex positivity, 64 patients with graft loss had a higher incidence of DSA or non-DSA antibodies than patients without graft loss (total: 59% vs. 36% ; p=0.013 ; class I: 50% vs. 31%, p=0.047 ; class II: 33% vs. 14%, p=0.021 ; DSA: 19% vs. 9%, p=0.20 ; non-DSA: 56% vs. 33%, p=0.013). Importantly, as many as 67% of Luminex-positive patients with graft loss were also positive in ELISA screening, whereas this rate was only 17% in the non-rejector group. In 51 patients with graft loss, we also had a pretransplant serum which allowed the evaluation of de novo antibody production after transplantation. The rate of de novo antibodies was higher in the graft loss group than in the non-rejector group (total DSA or non-DSA: 35% vs. 14%, p=0.020 ; class I: 29% vs. 10%, p=0.023 ; class II: 18% vs. 4%, p=0.051 ; DSA: 8% vs. 6%, p=n.s. ; non-DSA: 33% vs. 14%, p=0.034). Interestingly, at the low cut-off 500, as many as 45% of patients in the non-rejector group lost their preexisting DSA during the posttransplant course, as compared to only 25% in the graft loss group (p=0.062). Conclusion. Our data indicate that the posttransplant presence of strongly reactive HLA antibodies, especially if de novo produced, is associated with graft loss. It appears that not all Luminex-detected antibodies are detrimental. Many patients lose pretransplant weakly reactive donor-specific antibodies after transplantation and these antibodies are not associated with graft loss.

Kidney transplantation; graft loss; HLA antibodies

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