Dieterlen Maja-Theresa, John Katja, Bittner Hartmuth B, Mende Meinhard, Tarnok Attila, Mohr Friedrich W, Barten Markus J
Clinic for Cardiac Surgery, Heart Center Leipzig, University Hospital Leipzig, 04289 Leipzig, Germany.
Division of Thoracic Transplantation, Florida Hospital Orlando, Orlando, FL 32803, USA.
Dis Markers. 2015;2015:678061. doi: 10.1155/2015/678061. Epub 2015 Sep 30.
Pharmacodynamic biomarkers that detect changes of immunological functions have been recognized as a helpful tool to increase the efficacy of immunosuppressive drug therapies. However, physiological changes of immunological biomarkers following transplantation are not investigated. Therefore, we assessed frequently used immunological biomarkers of the circulating blood in the first year following heart transplantation (HTx).
Activation markers CD25 and CD95, intracellular cytokines IL-2 and IFNγ, chemokines IP10 and MIG, and subsets of dendritic cells as well as antibodies against human leukocyte antigens (HLA) and major histocompatibility complex class I-related chain A (MICA) antigens were analyzed at different time points using flow cytometry and Luminex xMAP technology.
Expression of IL-2, IFNγ, and plasmacytoid dendritic cells (pDCs) significantly increased (p < 0.01) during the first year. Anti-HLA antibodies decreased continuously, while anti-MICA antibodies showed minor increase within the first year. An association between percentage of pDCs and anti-MICA antibody positivity was proven. pDCs, IFNγ-producing T cells, and IP10 concentration were associated in a stronger way with age and gender of HTx recipients than with antibodies against HLA or MICA.
We conclude that certain immunological biomarkers of the circulating blood change during the first year after HTx. These changes should be considered for interpretation of biomarkers after transplantation.
能够检测免疫功能变化的药效学生物标志物已被视为提高免疫抑制药物治疗疗效的有用工具。然而,移植后免疫生物标志物的生理变化尚未得到研究。因此,我们评估了心脏移植(HTx)后第一年循环血液中常用的免疫生物标志物。
使用流式细胞术和Luminex xMAP技术在不同时间点分析活化标志物CD25和CD95、细胞内细胞因子IL-2和IFNγ、趋化因子IP10和MIG、树突状细胞亚群以及抗人类白细胞抗原(HLA)和主要组织相容性复合体I类相关链A(MICA)抗原的抗体。
在第一年中,IL-2、IFNγ和浆细胞样树突状细胞(pDCs)的表达显著增加(p < 0.01)。抗HLA抗体持续下降,而抗MICA抗体在第一年略有增加。已证实pDCs百分比与抗MICA抗体阳性之间存在关联。与抗HLA或MICA抗体相比,pDCs、产生IFNγ的T细胞和IP10浓度与HTx受者的年龄和性别关联更强。
我们得出结论,HTx后第一年循环血液中的某些免疫生物标志物会发生变化。在解释移植后的生物标志物时应考虑这些变化。