Anti-HLA antibodies are a major obstacle to transplantation success. We hypothesized that the complement binding capacity of anti-HLA antibodies assessed in the recipient sera could serve to stratify a population at risk for rejection and kidney allograft loss.
Patients who underwent kidney transplantation in 2 transplant centers in Paris (France) between Jan, 2004 and Jan, 2011 were included in our population-based study. All patients were tested for the presence of circulating donor-specific anti-HLA antibodies by SAFB techniques (DSA) and complement-fixing ability of these antibodies (C1q DSA) at the time of transplantation (Day0 DSA) and post-transplantation (1 year or at the time of biopsy proven acute rejection). The kidney graft injury phenotype and the time to allograft loss, were compared according to the presence of DSA and complement-fixing ability of these antibodies. Median follow-up after transplantation was 4.75 yrs (0.2-7).
1016 patients were included in the main analyses, of whom, 196 (19.3%) had Day0 DSA and 316 (31.1%) had post-transplant DSA. We identified 45 pts (23%) with C1q DSA at Day0 and 77 pts (24.4%) with post-transplant C1q DSA.
As compared to pts without C1q DSA at anytime, risk of graft loss was 11.6 times (95 CI 7.2-18.7) higher in pts who developed post-transplant C1q DSA, compared with an increase of 5.8 (2.6-12.7, p<.001) in pts with persisting C1q DSA and no significant rise in pts with negativation of C1q DSA after transplantation (HR 2.6, 0.8-8.4, p=0.1).
After adjusting for DSA and C1q status at Day0 and post-transplantation in a multivariate Cox model, the presence of post-transplant C1q DSA remained strongly associated with a higher risk of graft loss (HR 6.3, 3.2-11.2, p<.0001). Of these patients with post-transplant C1q DSA, 67 (87%) had microcirculation inflammation, 28 (36%) had interstitial and tubular inflammation and 47 (61%) had C4d deposition.
Complement-fixing anti-HLA DSA detected post-transplantation identifies a group of kidney recipients with the highest risk of graft loss. The determination of complement fixing capability of DSAs allows risk stratification that may help guiding clinical management of kidney recipients.
To cite this abstract in AMA style:Lefaucheur C, Loupy A, Vernerey D, Suberbielle C, Jouven X, Legendre C, Glotz D, Zeevi A. Post-Transplant Complement Binding DSA: Higher Risk of Kidney Allograft Loss [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/post-transplant-complement-binding-dsa-higher-risk-of-kidney-allograft-loss/. Accessed June 14, 2021.
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