Longitudinal profile of circulating T follicular helper lymphocytes parallels anti-HLA sensitization in renal transplant recipients
Longitudinal profile of circulating T follicular helper lymphocytes parallels anti-HLA sensitization in renal transplant recipients
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DOI：
10.1111/ajt.14987
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发表时间：
2019-01-01
影响因子：
8.8
通讯作者：
Paz-Artal, Estela
中科院分区：
文献类型：
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作者：
Luis Cano-Romero, Francisco;Laguna Goya, Rocio;Paz-Artal, Estela
抗体介导的排斥反应导致30%-50%的肾移植失败。B细胞分化为产生抗体的浆母细胞取决于滤泡辅助性T细胞（Tfh）的协同作用。我们分析了肾受体的循环Tfh (cTfh)，并研究了cTfh与抗hla抗体产生和移植结果的关系。cTfh在移植前和移植后的前瞻性队列患者（n = 206）中进行纵向分析。记录临床资料、HLA致敏、cTfh功能。移植前和移植后6个月的cTfh均能获得产生igg的质母细胞。移植前cTfh在患者中降低，尤其是接受透析的患者。然而，这些细胞在先前接受同种异体移植或输血的患者和hla敏感受体中增加。移植后cTfh扩大，在产生新抗hla抗体的患者中明显多于未致敏的患者。移植前cTfh增高与移植前抗hla I类抗体强度增高以及新生抗hla I类和抗hla II类抗体呈正相关。同样，急性排斥反应患者的移植前cTfh较高（HR = 1.14[1.04-1.25]）。因此，我们发现Tfh在抗hla致敏和排斥反应中的作用。需要更多患者队列的多中心研究来验证这些结果。针对Tfh的免疫抑制药物可能有助于改善预后。
Antibody-mediated rejection is responsible for 30%-50% of renal graft failures. Differentiation of B cells into antibody-producing plasmablasts depends on the collaboration of follicular helper T cells (Tfh). We analyzed circulating Tfh (cTfh) in kidney recipients and studied cTfh relationship with anti-HLA antibody production and graft outcome. cTfh were longitudinally analyzed in a prospective cohort of patients (n = 206), pre- and posttransplantation. Clinical data, HLA sensitization, and cTfh function were recorded. Both pretransplant and 6-month posttransplant cTfh were able to derive IgG-producing plasmablasts. Pretransplant cTfh was decreased in patients, especially in those who received dialysis. However, these cells were increased in patients with previous allograft or transfusions and in HLA-sensitized recipients. After transplantation cTfh expanded, significantly more in patients who developed de novo anti-HLA antibodies than in patients who remained unsensitized. Augmented pretransplant cTfh positively correlated with higher intensity of pretransplant anti-HLA class I and with de novo anti-HLA class I and anti-HLA class II antibodies. Consistently, pretransplantation cTfh were higher in patients who experienced acute rejection (HR = 1.14 [1.04-1.25]). Thus, we show a role for Tfh in anti-HLA sensitization and rejection. Multicenter studies with additional patient cohorts are needed to validate these results. Immunosuppressive drugs targeting Tfh could be useful to improve outcomes.