Pre-transplant assessment of pp65-specific CD4 T cell responses identifies CMV-seropositive patients treated with rATG at risk of late onset infection.

pp65-specific CD4 + T细胞应答的移植前评估鉴定了用rATG治疗的CMV血清阳性患者具有迟发性感染的风险。

  • 影响因子:3.12
  • DOI:10.1016/j.clim.2019.108329
  • 作者列表:"López-Oliva MO","Martínez V","Rodríguez-Sanz A","Álvarez L","Santana MJ","Selgas R","Jiménez C","Bellón T
  • 发表时间:2020-02-01

:Assessment of CMV-specific T cell immunity might be a useful tool in predicting CMV infection after solid organ transplantation. We have investigated CD4 and CD8 T-cell responses to CMV pp65 and IE-1 antigens in a prospective study of 28 CMV-seropositive kidney transplant recipients who were administered lymphocyte-depleting antibodies (Thymoglobulin®) as induction treatment and with universal prophylaxis for CMV infection. The response was analyzed by intracellular flow cytometry analysis of IFN-γ production in pretransplant samples and at 1, 6, 12 and 24 months post-transplant. Overall, only pretransplant CD4 T-cell responses to pp65 were significantly lower (p = .004) in patients with CMV replication post-transplant. ROC curve analysis showed that pre-transplant frequencies of pp65-specific CD4 + T cells below 0.10% could predict CMV infection with 75% sensitivity and 83.33% specificity (AUC: 0.847; 95% CI: 0.693-1.001; p = .0054) and seem to be mandatory for efficient control of CMV viral replication by the host immune system. In conclusion, the functional assessment of CMV-specific CD4 T-cell immunity pretransplant in seropositive patients may allow the identification of Thymoglobulin®-treated kidney transplant recipients at risk of developing CMV infection post-transplantation.


: 评估CMV特异性T细胞免疫可能是预测实体器官移植后CMV感染的有用工具。我们研究了CD4和CD8 T细胞对CMV pp65和IE-1抗原的反应,对28例CMV血清阳性肾移植受者进行了一项前瞻性研究,这些受者接受了淋巴细胞消耗抗体 (胸腺球蛋白®) 作为CMV感染的诱导治疗和普遍预防。通过细胞内流式细胞术分析移植前样品和移植后1、6、12和24个月时IFN-γ 产生的反应。总体而言,只有移植前cd4t细胞对pp65的反应在移植后具有CMV复制的患者中显著较低 (p =.004)。ROC曲线分析显示,pp65-specific CD4 + t细胞移植前频率低于0.10% 可预测CMV感染,灵敏度为75%,特异度为83.33% (AUC: 0.847; 95% CI: 0.693-1.001; P =.0054) 并且似乎是通过宿主免疫系统有效控制CMV病毒复制的强制性要求。总之,血清阳性患者移植前CMV特异性CD4 T细胞免疫的功能评估可能允许鉴定胸腺球蛋白®-接受治疗的肾移植受者在移植后有发生CMV感染的风险。



作者列表:["Mac K","Hedley J","Kelly PJ","Lee VW","Agar JWM","Hawley CM","Johnson DW","See EJ","Polkinghorne KR","Rabindranath KS","Sud K","Webster AC"]

METHODS:BACKGROUND:The use of haemodiafiltration (HDF) for the management of patients with end-stage kidney failure is increasing worldwide. Factors associated with HDF use have not been studied and may vary in different countries and jurisdictions. The aim of this study was to document the pattern of increase and variability in uptake of HDF in Australia and New Zealand, and to describe patient- and centre-related factors associated with its use. METHODS:Using the Australian and New Zealand Dialysis and Transplant Registry, all incident patients commencing haemodialysis (HD) between 2000 and 2014 were included. The primary outcome was HDF commencement over time, which was evaluated using multivariable logistic regression stratified by country. RESULTS:Of 27 433 patients starting HD, 3339 (14.4%) of 23 194 patients in Australia and 810 (19.1%) of 4239 in New Zealand received HDF. HDF uptake increased over time in both countries but was more rapid in New Zealand than Australia. In Australia, HDF use was more likely in males (odds ratio (OR) 1.13, 95% confidence interval (CI) = 1.03-1.24, P = 0.009) and less likely with older age (reference <40 years; 40-54 years OR = 0.85; 95% CI = 0.72-0.99; 55-69 years OR = 0.79; 95% CI = 0.67-0.91; >70 years OR = 0.48; 95% CI = 0.41-0.56); higher body mass index (body mass index (BMI) < 18.5 kg/m2 OR = 0.62; 95% CI = 0.46-0.84; 18.5-29.9 kg/m2 reference; >30 kg/m2 OR = 1.46; 95% CI = 1.33-1.61), chronic lung disease (OR = 0.84; 95% CI = 0.76-0.94; P < 0.001), cerebrovascular disease (OR = 0.76; 95% CI = 0.67-0.85; P < 0.001) and peripheral vascular disease (OR = 0.77; 95% CI = 0.70-0.85; P < 0.001). No association was identified with race. In New Zealand, HDF use was more likely in Maori and Pacific Islanders (OR = 1.32; 95% CI = 1.05-1.66) and Asians (OR = 1.75; 95% CI = 1.15-2.68) compared to Caucasians, and less likely in males (OR = 0.76; 95% CI = 0.62-0.94; P = 0.01). No association was identified with BMI or co-morbidities. In both countries, centres with a higher ratio of HD to peritoneal dialysis (PD) were more likely to prescribe HDF. Larger Australian centres were more likely to prescribe HDF (36-147 new patients/year OR = 26.75, 95% CI = 18.54-38.59; 17-35/year OR = 7.51, 95% CI = 5.35-10.55; 7-16/year OR = 3.00; 95% CI = 2.19-4.13; ≤6/year reference). CONCLUSION:Haemodiafiltration uptake is increasing, variable and associated with both patient and centre characteristics. Centre characteristics not explicitly captured elsewhere explained 36% of variability in HDF uptake in Australia and 48% in New Zealand.

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作者列表:["Touzot M","Seris P","Maheas C","Vanmassenhove J","Langlois AL","Moubakir K","Laplanche S","Petitclerc T","Ridel C","Lavielle M"]

METHODS:AIM:Clinical interpretation of B-type natriuretic peptide (BNP) levels in haemodialysis (HD) patients for fluid management remains elusive. METHODS:We conducted a retrospective observational monocentric study. We built a mathematical model to predict BNP levels, using multiple linear regressions. Fifteen clinical/biological characteristics associated with BNP variation were selected. A first cohort of 150 prevalent HD (from September 2015 to March 2016) was used to build several models. The best model proposed was internally validated in an independent cohort of 75 incidents HD (from March 2016 to December 2017). RESULTS:In cohort 1, mean BNP level was 630 ± 717 ng/mL. Cardiac disease (CD - stable coronary artery disease and/or atrial fibrillation) was present in 45% of patients. The final model includes age, systolic blood pressure, albumin, CD, normo-hydrated weight (NHW) and the fluid overload (FO) assessed by bio-impedancemetry. The correlation between the measured and the predicted log-BNP was 0.567 and 0.543 in cohorts 1 and 2, respectively. Age (β = 3.175e-2 , P < 0.001), CD (β = 5.243e-1 , P < 0.001) and FO (β = 1.227e-1 , P < 0.001) contribute most significantly to the BNP level, respectively, but within a certain range. We observed a logistic relationship between BNP and age between 30 and 60 years, after which this relationship was lost. BNP level was inversely correlated with NHW independently of CD. Finally, our model allows us to predict the BNP level according to the FO. CONCLUSION:We developed a mathematical model capable of predicting the BNP level in HD. Our results show the complex contribution of age, CD and FO on BNP level.

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作者列表:["Yeh EL","Chen CH","Huang SC","Huang YC"]

METHODS:AIM:The removal of cysteine during a dialysis procedure may affect glutathione (GSH) concentration, allowing haemodialysis (HD) patients to become more susceptible to oxidative damage. This study was performed to determine whether the change of GSH/glutathione disulfide (GSSG) redox state and GSH redox potential were linked with the change of cysteine or oxidative stress in patients receiving HD treatment. METHODS:Sixty-seven HD patients who had received regular HD treatment were recruited. Plasma GSH, GSSG, cysteine and malondialdehyde (MDA) were measured at both pre- and post-HD. RESULTS:Plasma cysteine, GSH and GSSG levels significantly decreased after the completion of HD, compared to the levels at pre-HD. Plasma MDA concentration, GSH/GSSG ratio and GSH redox potential remained constant during the dialysis session. Plasma GSH and GSSG were positively associated with plasma MDA at post-HD, while GSH redox potential was negatively associated with plasma MDA at post-HD. However, plasma GSH, GSSG, GSH/GSSG ratio and GSH redox potential were not associated with plasma cysteine at either pre- or post-HD. CONCLUSION:The GSH and GSSG levels were significantly utilized during a HD session, and their levels were significantly associated with increased oxidative stress. HD patients may require higher GSH demands to cope with increased oxidative stress during an HD session.

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