9-O-乙酰神经节苷脂 D3（CD60）和α4β1（CD49d）表达在预测蕈样肉芽肿患者生存中的作用。
The role of 9-O-acetylated ganglioside D3 (CD60) and {alpha}4{beta}1 (CD49d) expression in predicting the survival of patients with Sezary syndrome.
机构信息
Center for Molecular Allergology, IDI-IRCCS, Via dei Monti di Creta 104, I-00167 Rome, Italy.
出版信息
Haematologica. 2010 Nov;95(11):1905-12. doi: 10.3324/haematol.2010.026260. Epub 2010 Jul 27.
BACKGROUND
Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4(+) T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×10(9)/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described.
DESIGN AND METHODS
We used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4(+) T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan-Meier product-limit estimates and hazard ratios from the Cox proportional hazards model.
RESULTS
We found that both higher number of CD60(+) and lower number of CD49d(+) cells within circulating CD4(+) T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4(+)CD60(+) cells (≥ 0.5×10(9)/L) and low proportion of CD4(+)CD49d(+) cells (<0.5×10(9)/L) (hazard ratio = 12.303, 95% confidence interval 1.5-95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1.
CONCLUSIONS
In this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4(+) T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome.
背景
蕈样肉芽肿是一种罕见且极具侵袭性的皮肤 T 细胞淋巴瘤的白血病变体，其特征为广泛的皮肤受累以及恶性循环 CD4(+)T 细胞克隆，该克隆归巢至皮肤，过度表达 CD60，并且缺乏 CD7、CD26 和 CD49d。迄今为止，该疾病的预后标志物仅限于全身性皮质类固醇治疗、年龄、血清乳酸脱氢酶和白细胞计数 20×10(9)/L 或更高：尚未描述具有预后价值的其他生物标志物，尤其是与恶性细胞相关的生物标志物。
设计和方法
我们使用流式细胞术分析比较了 62 例蕈样肉芽肿患者、180 例真菌性皮肤病患者、6 例 B 细胞淋巴瘤患者和 19 例慢性湿疹患者循环 CD4(+)T 细胞群体中 T 细胞受体-Vβ 谱系和几种表面分子（CD7、CD26、CD49d 和 CD60）的分布。我们使用 Kaplan-Meier 乘积限估计和 Cox 比例风险模型的风险比计算首次住院后蕈样肉芽肿患者的 5 年总生存率。
结果
我们发现，疾病发作时循环 CD4(+)T 细胞中 CD60(+)细胞数量增加和 CD49d(+)细胞数量减少与生存率降低显著相关。对于 CD4(+)CD60(+)细胞比例高（≥0.5×10(9)/L）和 CD4(+)CD49d(+)细胞比例低（<0.5×10(9)/L）的患者，观察到极高的死亡风险（风险比=12.303，95%置信区间 1.5-95.9；P<0.02）。此外，61.9%的蕈样肉芽肿患者的循环 T 细胞克隆中观察到 T 细胞受体-Vβ 亚家族的偏倚性使用，T 细胞受体-Vβ 2 和 5.1 亚家族最为常见（42.8%），其次是 T 细胞受体-Vβ 12 和 13.1。
结论
在这项研究中，我们表明循环 CD4(+)T 细胞上 CD60 的上调和 CD49d 的下调是预测蕈样肉芽肿患者预后非常差的两个有用标志物。
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