Liang Emily C, Rossetti Maura, Sidwell Tiffany, Groysberg Victoria, Sunga Gema, Korin Yael, Vangala Sitaram, Abdalla Basmah, Lum Erik, Bunnapradist Suphamai, Pham Phuong-Thu, Danovitch Gabriel, Reed Elaine F, Schaenman Joanna
Division of Infectious Diseases, Department of Medicine, University of California Los Angeles Immunogenetics Center, Los Angeles, CA.
Department of Pathology and Laboratory Medicine, University of California Los Angeles Immunogenetics Center, Los Angeles, CA.
Transplant Direct. 2018 Feb 14;4(3):e348. doi: 10.1097/TXD.0000000000000762. eCollection 2018 Mar.
The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes.
Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression.
Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16-) (94.5% vs 92.1%) ( = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients.
In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation.
需要肾移植的终末期肾病老年患者数量持续增加。对健康老年人的评估显示免疫系统存在促炎变化，据推测这些变化通过“炎症衰老”导致与年龄相关的疾病。免疫功能障碍也与感染控制受损有关。目前尚不清楚这些免疫变化是否在老年肾移植受者中存在，但可能对不良临床结局的风险具有重要意义。
移植后三个月，通过流式细胞术对60名肾移植受者（22名老年患者[≥60岁]和38名年轻患者[<60岁]）的天然免疫表型进行评估。采用多重细胞因子检测来评估血浆细胞因子水平。根据移植类型和诱导免疫抑制情况，将年轻患者与老年患者进行匹配。
与年轻患者相比，老年肾移植受者的中间单核细胞（CD14++CD16+）频率降低（1.2%对3.3%，P = 0.007），促炎经典单核细胞（CD14++CD16-）频率有增加趋势（94.5%对92.1%）（P = 0.065）。老年患者的干扰素-γ（IFN-γ）水平升高。
在这项肾移植受者的初步研究中，我们发现老年患者与年轻患者相比，天然免疫系统存在差异，包括IFN-γ水平升高。这表明尽管进行了免疫抑制，与年龄相关的非特异性炎症仍然存在。对移植受者应用非侵入性检测的能力将为患者风险分层和免疫抑制方案个体化提供工具，以改善移植后的结局。
