Cuesta-Martín de la Cámara Ricardo, Miguel-Berenguel Laura, Cámara Carmen, Losantos-García Itsaso, Frauca-Remacha Esteban, Hierro-Llanillo Loreto, Muñoz-Bartolo Gema, Lledín-Barbacho María Dolores, Martínez-Feito Ana, López-Granados Eduardo, Sánchez-Zapardiel Elena
Clinical Immunology Department, University Hospital La Paz, Madrid, Spain.
Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.
Front Immunol. 2025 Jun 12;16:1605716. doi: 10.3389/fimmu.2025.1605716. eCollection 2025.
Immune monitoring has been proposed to optimize immunosuppressive therapy in liver recipients. This study aims to describe immunological changes following liver transplantation in pediatric recipients and to identify immune markers associated with post-transplant complications.
The immunological status of 95 pediatric liver recipients was prospectively assessed before transplantation and at 1, 3, 6, 9 and 12 months post-transplantation. Serum immunoglobulins (Ig) were measured by nephelometry and immunophenotype was evaluated by flow cytometry. T, B and NK lymphocyte counts were adjusted for age using standard reference ranges.
Graft rejection, post-transplant lymphoproliferative disorder and autoimmune hepatitis was diagnosed in 6%, 2% and 0% patients, respectively. Early infections affected 43% patients, while late infections occurred in 17%, 24%, 10% and 9% recipients at each follow-up interval. Baseline immune dysregulation primarily involved the cellular compartment, with 78% recipients showing lymphopenia. Lymphocyte subpopulation scores improved following liver transplantation, with CD4 score normalizing by month 1 and CD8, CD19 and NK scores by month 6. First-month IgG hypogammaglobulinemia, observed in 20% recipients, resolved completely at month 12. First-month T-cell lymphopenia (CD3 hazard ratio [HR] 2.48, p=0.005; CD8 HR 2.38, p=0.008) and hypogammaglobulinemia (IgG HR 2.18, p=0.036; IgA HR 2.40, p=0.011; IgM HR 2.61, p=0.006) were associated with higher risk of late infections. In multivariate analysis, only CD3 T-cell lymphopenia remained a significant predictor (HR 2.13, p=0.030).
Baseline immune dysregulation resolved within the first months post-transplantation. Early infections were unrelated to immune markers, while late infections were associated with CD3 T-cell lymphopenia and hypogammaglobulinemia.
免疫监测已被提议用于优化肝移植受者的免疫抑制治疗。本研究旨在描述小儿肝移植受者移植后的免疫变化,并确定与移植后并发症相关的免疫标志物。
前瞻性评估95名小儿肝移植受者在移植前以及移植后1、3、6、9和12个月时的免疫状态。采用散射比浊法测定血清免疫球蛋白(Ig),并通过流式细胞术评估免疫表型。使用标准参考范围对T、B和NK淋巴细胞计数进行年龄校正。
分别有6%、2%和0%的患者被诊断为移植物排斥、移植后淋巴细胞增生性疾病和自身免疫性肝炎。早期感染影响43%的患者,而在每个随访间隔期,晚期感染分别发生在17%、24%、10%和9%的受者中。基线免疫失调主要涉及细胞部分,78%的受者表现为淋巴细胞减少。肝移植后淋巴细胞亚群评分有所改善,CD4评分在第1个月恢复正常,CD8、CD19和NK评分在第6个月恢复正常。20%的受者在第1个月出现IgG低丙种球蛋白血症,在第12个月时完全缓解。第1个月的T细胞淋巴细胞减少(CD3风险比[HR] 2.48,p = 0.005;CD8 HR 2.38,p = 0.008)和低丙种球蛋白血症(IgG HR 2.18,p = 0.036;IgA HR 2.40,p = 0.011;IgM HR 2.61,p = 0.006)与晚期感染的较高风险相关联。在多变量分析中,只有CD3 T细胞淋巴细胞减少仍然是一个显著的预测因素(HR 2.13,p = 0.030)。
基线免疫失调在移植后的头几个月内得到缓解。早期感染与免疫标志物无关,而晚期感染与CD3 T细胞淋巴细胞减少和低丙种球蛋白血症相关。