Department of Internal Medicine and Gerontology, Jagiellonian University/University Hospital, Cracow, Poland.
Immunobiology. 2013 May;218(5):810-6. doi: 10.1016/j.imbio.2012.09.003. Epub 2012 Oct 4.
Adult survivors of childhood malignancy are prone to accelerated atherogenesis and late cardiovascular complications. Plaque formation is initiated by recruitment of monocytes and T-cells into the intima, mediated by adhesion molecules and chemokines expressed by activated endothelial cells.
To assess markers of inflammatory activity, endothelial activation as well as monocyte heterogeneity in adult survivors of childhood acute lymphoblastic leukemia (ALL) who had been treated with chemotherapy without cranial irradiation.
We studied 27 (age: 18-28 years) healthy survivors of childhood ALL and 20 controls (age: 20-31 years). Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes which were further characterized by their expression of HLA-DR and β2-integrins CD11b/CD18 and CD11c/CD18. In ALL survivors we found increased levels of pentraxin-3 (median [interquartile range]: 0.63 [0.36-0.94] vs. 0.40 [0.32-0.57] ng/ml; p = 0.03), soluble vascular cell adhesion molecule-1 (687 [597-761] vs. 558 [534-702]ng/ml; p = 0.02), osteoprotegerin (mean ± SD: 5.24 ± 1.00 vs. 4.42 ± 1.34 pmol/l; p = 0.02) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (107.0 ± 23.6 vs. 89.5 ± 18.9 pg/ml; p = 0.01), whereas C-reactive protein, interleukin 6 and 18, TNF-α, monocyte chemotactic protein-1 and soluble intercellular adhesion molecule-1 were unchanged. Former ALL patients exhibited elevated counts of intermediate monocytes (6.3 ± 4.0 vs. 4.3 ± 1.5% of blood monocytes; p = 0.03). CD11b/CD18 and CD11c/CD18 expression on intermediate monocytes tended to be higher in ALL survivors (1917 ± 993 vs. 1396 ± 673 MFI [median fluorescence intensity]; p = 0.06 and 3883 ± 1445 vs. 3185 ± 645 MFI; p = 0.05, respectively).
Our findings suggest chronic inflammatory activation and immune dysregulation in adult survivors of childhood ALL, which can translate into late cardiovascular morbidity.
儿童期恶性肿瘤的成年幸存者易发生动脉粥样硬化加速和晚期心血管并发症。斑块形成是由激活的内皮细胞表达的黏附分子和趋化因子募集单核细胞和 T 细胞进入内膜而引发的。
评估未接受颅照射的化疗治疗的儿童期急性淋巴细胞白血病 (ALL) 成年幸存者的炎症活动、内皮激活和单核细胞异质性的标志物。
我们研究了 27 名（年龄：18-28 岁）健康的儿童 ALL 幸存者和 20 名对照者（年龄：20-31 岁）。使用流式细胞术鉴定单核细胞亚群：经典 CD14(++)CD16(-)、中间 CD14(++)CD16(+)和非经典 CD14(+)CD16(++)单核细胞，进一步通过其表达 HLA-DR 和 β2-整联蛋白 CD11b/CD18 和 CD11c/CD18 来鉴定。在 ALL 幸存者中，我们发现 pentraxin-3（中位数[四分位数范围]：0.63 [0.36-0.94] vs. 0.40 [0.32-0.57] ng/ml；p = 0.03）、可溶性血管细胞黏附分子-1（687 [597-761] vs. 558 [534-702]ng/ml；p = 0.02）、骨保护素（平均±标准差：5.24 ± 1.00 vs. 4.42 ± 1.34 pmol/l；p = 0.02）和肿瘤坏死因子（TNF）相关凋亡诱导配体（107.0 ± 23.6 vs. 89.5 ± 18.9 pg/ml；p = 0.01）水平升高，而 C 反应蛋白、白细胞介素 6 和 18、TNF-α、单核细胞趋化蛋白-1 和可溶性细胞间黏附分子-1 没有变化。既往 ALL 患者中间单核细胞计数升高（6.3 ± 4.0 vs. 4.3 ± 1.5%的血液单核细胞；p = 0.03）。ALL 幸存者中间单核细胞上的 CD11b/CD18 和 CD11c/CD18 表达趋于升高（1917 ± 993 vs. 1396 ± 673 MFI[荧光强度中位数]；p = 0.06 和 3883 ± 1445 vs. 3185 ± 645 MFI；p = 0.05，分别）。
我们的研究结果表明，儿童期 ALL 成年幸存者存在慢性炎症激活和免疫失调，这可能导致晚期心血管发病率增加。
