The development of donor‐specific HLA antibodies (DSA) is associated with worse renal allograft survival in adult patients. This study assessed the natural history of de novo DSA, and its impact on renal function in pediatric renal transplant recipients (RTR). HLA antibodies were measured prospectively using single‐antigen‐bead assays at 1, 3, 6 and 12 months posttransplant followed by 12‐monthly intervals and during episodes of allograft dysfunction. Of 215 patients with HLA antibody monitoring, 75 (35%) developed DSA at median of 0.25 years posttransplant with a high prevalence of Class II (70%) and HLA‐DQ (45%) DSA. DSA resolved in 35 (47%) patients and was associated with earlier detection (median, inter‐quartile range 0.14, 0.09–0.33 vs. 0.84, 0.15–2.37 years) and lower mean fluorescence intensity (MFI) (2658, 1573–3819 vs. 7820, 5166–11 990). Overall, DSA positive patients had more rapid GFR decline with a 50% reduction in GFR at mean 5.3 (CI: 4.7–5.8) years versus 6.1 (5.7–6.4) years in DSA negative patients (p = 0.02). GFR decreased by a magnitude of 1 mL/min/1.73 m2 per log10 increase in Class II DSA MFI (p < 0.01). Using Cox regression, independent factors predicting poorer renal allograft outcome were older age at transplant (hazard ratio 1.1, CI: 1.0–1.2 per year), tubulitis (1.5, 1.3–1.8) and microvasculature injury (2.9, 1.4–5.7). In conclusion, pediatric RTR with de novo DSA and microvasculature injury were at risk of allograft failure.

UK National Health Service Blood & Transplant and Guy's & St Thomas' National Institute for Health Research Biomedical Research Centre.

This paper provides information about the prevalence and topography of self-injurious behavior in children and adults with autism spectrum disorder and intellectual disability. Dominant models regarding the etiology of self-injury in this population are reviewed, with a focus on the role of reactivity to pain and sensory input. Neuroimaging studies are presented and suggestions are offered for future research.

SummaryGraft survival seems to be worse in positive cross-match (HLAi) than in ABOincompatible (ABOi) transplantation. However, it is not entirely clear why these differences exist. Sixty-nine ABOi, 27 HLAi and 10 combined ABOi+HLAi patients were included in this retrospective study, to determine whether the frequency, severity and the outcome of active antibody-mediated rejection (AMR) were different. Five-year death-censored graft survival was better in ABOi than in HLAi and ABOi+HLAi patients (99%, 69% and 64%, respectively, P = 0.0002). Features of AMR were found in 38%, 95% and 100% of ABOi, HLAi and ABOi+HLAi patients that had a biopsy, respectively (P = 0.0001 and P = 0.001). After active AMR, a declining eGFR and graft loss were observed more frequently in HLAi and HLAi+ABOi than in ABOi patients. The poorer prognosis after AMR in HLAi and ABOi+HLAi transplantations was not explained by a higher severity of histological lesions or by a less aggressive treatment. In conclusion, ABOi transplantation offers better results than HLAi transplantation, partly because AMR occurs less frequently but also because outcome after AMR is distinctly better. HLAi and combined ABOi+HLAi transplantations appear to have the same outcome, suggesting there is no synergistic effect between anti-A/B and anti-HLA antibodies.

IntroductionWe have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes.MethodsA total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator.ResultsOf 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R 2 0.072; C3d: adjusted R 2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04].ConclusionAssessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction.Electronic supplementary materialThe online version of this article (10.1007/s00467-017-3772-7) contains supplementary material, which is available to authorized users.