De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients

Abstract

De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients, dnDSAs developed within 1 year (early-onset group), while the other 24 seroconverted after the first posttransplant year (late-onset group). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlier dnDSA development. Late AMR was diagnosed in 47% of the early group and in 58% of the late group. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients in early- and late-onset groups, respectively (p = ns). In our pediatric kidney recipients, dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence.

Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients

“…[29][30][31][32] Biopsy or necropsy findings were analyzed both individually and in functional clusters. [33][34][35][36] Statistical Analyses Statistical analyses were performed using Prism 7.0 and 8.0 (GraphPad Software, San Diego, CA). Values of P,0.05 were considered to be statistically significant.…”

Application, technical issues, and interpretation of C1q for graft outcome

“…As graft loss occurred about 2 years post dnDSA detection, they recommended treating when dnDSA was first detected since monitoring would be expensive. In a similar cohort stratified by early (less than 1 year) and late (more than 1 year) dnDSA detection, Cioni et al [ 28 ] reported 47% AMR+ and 20% subsequent graft loss in the early group; 80% of which were C1q+.…”

Application and interpretation of histocompatibility data in pediatric kidney transplantation

“…In an Italian cohort of 114 pediatric transplant recipients, 39 patients developed dn DSA, 15 of which developed early dn DSA, before the first year post-transplant. 34 Regardless of timing of appearance, dn DSA was associated with late antibody mediated rejection in 47% of early group and 58% of the late group, and allograft loss occurred in early and late dn DSA groups (20% and 17%, respectively) in a median follow-up time of 6.7 years.…”