Research Group Epidemiological and Statistical Methods (ESME), Helmholtz Centre for Infection Research, Braunschweig, Germany.
Division of Pediatric Gastroenterology and Hepatology, Department of Paediatric Liver, Kidney and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Front Immunol. 2019 Jan 25;10:52. doi: 10.3389/fimmu.2019.00052. eCollection 2019.
Both, markers of cellular immunity and serum cytokines have been proposed as potential biomarkers for graft rejection liver transplantation. However, no good prognostic model is available for the prediction of acute cellular rejection. The impact of underlying disease and demographic factors on immune status pediatric liver transplantation (pLTx) is still poorly understood. We investigated expression of immune markers before pLTx, in order to better understand the pre-transplant immune status. Improved knowledge of the impact of pre-transplant variables may enhance our understanding of immunological changes post pLTx in the future. This is a cross-sectional analysis of data from the ChilSFree study, a European multicentre cohort study investigating the longitudinal patterns of immune response before and after pLTx. Immune cell counts and soluble immune markers were measured in 155 children 1-30 days before pLTx by TruCount analysis and BioPlex assays. Results were logarithmised due to skewed distributions and then compared according to age, sex, and diagnosis using -tests, ANOVAs, and Tukey tests. The association between immune markers at time of pLTx and patients' age was assessed using a fractional polynomial approach. Multivariable regression models were used to assess the relative contribution of each factor. Sex had no effect on immune status. We found strong evidence for age-specific differences in the immune status. The majority of immune markers decreased in a log-linear way with increasing age. T and B cells showed a sharp increase within the first months of life followed by a log-linear decline in older age groups. Several immune markers were strongly associated with underlying diagnoses. The effects of age and underlying disease remained virtually unchanged when adjusting for each other in multivariable models. We show for the first time that age and diagnosis are major independent determinants of cellular and soluble immune marker levels in children with end-stage liver disease. These results need to be considered for future research on predictive immune monitoring after pLTx.
细胞免疫标志物和血清细胞因子均被认为是肝移植排斥反应的潜在生物标志物。然而，目前尚无用于预测急性细胞排斥反应的良好预后模型。潜在疾病和人口统计学因素对小儿肝移植（pLTx）免疫状态的影响仍知之甚少。我们研究了 pLTx 前免疫标志物的表达，以便更好地了解移植前的免疫状态。更好地了解移植前变量的影响可能会增强我们对未来 pLTx 后免疫变化的理解。
这是 ChilSFree 研究的横断面数据分析，该研究是一项欧洲多中心队列研究，调查了 pLTx 前后免疫反应的纵向模式。在 pLTx 前 1-30 天，通过 TruCount 分析和 BioPlex 测定法测量了 155 名儿童的免疫细胞计数和可溶性免疫标志物。由于偏态分布，结果进行了对数化，然后使用 t 检验、方差分析和 Tukey 检验根据年龄、性别和诊断进行比较。使用分数多项式方法评估 pLTx 时免疫标志物与患者年龄之间的相关性。使用多变量回归模型评估每个因素的相对贡献。
性别对免疫状态没有影响。我们发现免疫状态存在明显的年龄特异性差异。大多数免疫标志物随年龄的增长呈对数线性下降。T 和 B 细胞在生命的最初几个月中急剧增加，然后在年龄较大的年龄组中呈对数线性下降。几种免疫标志物与潜在诊断密切相关。在多变量模型中相互调整时，年龄和潜在疾病的影响几乎保持不变。
我们首次表明，年龄和诊断是终末期肝病儿童细胞和可溶性免疫标志物水平的主要独立决定因素。这些结果需要在未来的 pLTx 后预测性免疫监测研究中加以考虑。
