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.

Anti‐HLA‐antibody characteristics aid to risk‐stratify patients and improve long‐term renal graft outcomes. Complement activation by donor‐specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross‐match‐positive). We explored the role of C3d‐positive DSAs in sub‐stratification of cross‐match‐positive cases and relate to the graft outcomes. We investigated 139 cross‐match‐positive living‐donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post‐transplant. C3d‐positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post‐transplant. Median follow‐up of patients was 48 months (IQR 20.47–77.57). In the multivariable analysis, pretreatment C3d‐positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37–7.86). The relative risk of death‐censored five‐year graft failure was 2.83 (95% CI 1.56–5.13). Patients with both pretreatment and Day 14 C3d‐positive DSAs had the worst five‐year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d‐negative DSA patients with the relative risk of death‐censored five‐year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub‐stratify the risk of poor graft outcome in cross‐match‐positive living‐donor renal transplantation.

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Background Eosinophilic esophagitis (EoE) is a clinicopathological disease characterised by oesophageal eosinophilia and gastrointestinal symptoms. It is caused by immunologic reactions to ingested and inhaled allergens. The diagnosis is considered if at least 15 eosinophils are detected per high-powered field in mucosal biopsies. Purpose To describe and evaluate the efficacy of oral viscous budesonide for EoE in paediatric patients. Materials and methods Patient, 11 years old, diagnosed with EoE, persistent atopic asthma and pollen rhinoconjunctivitis, with multiple food allergies. He initiated a restricted-foods diet and drug treatment with Montelukast 10 mcg/24 h, Fluticasone 50 mcg twice daily and on-demand salbutamol inhalation, which failed, although there was some clinical improvement. Therefore, treatment with budesonide suspension was initiated 0.5 mcg twice daily, 1 h after meals. Budesonide suspension is a viscous liquid consisting of budesonide nebulizer suspension (Pulmicort respules 0.50mg/ml) mixed with sodium benzoate sodium, saccharin, and glycerine with constant stirring until blended. Finally add the strawberry essence and incorporate xanthan gum on top without mixing and add water to 240 ml. The final concentration is 0.25 mg/ml. Results In our present medical case, the patient presented eosinophilic enteritis and esophagitis, despite having been treated with omeprazole, antihistamines, and dietary advice. Between April 2013 and May 2013, he had been receiving, budesonide 500 mcg/12 hourly and dietary treatment. He had a significant improvement. After the treatment the endoscopy was completely normalised. Unfortunately, 3 months later after stopping the oral steroids the patient reported recurrence of symptoms. Conclusions As with most eosinophilic diseases, oral steroids improve oesophageal eosinophilic and symptoms in patients with EoE. Treatment with budesonide induced full remission in the patient. Unfortunately, the therapeutic effect of oral steroids on the disease is abolished following cessation of treatment. Therefore, patients may have to continue on therapeutic treatment levels for an indefinite amount of time No conflict of interest.