Serum soluble CD48 levels as a prognostic marker in mycosis fungoides and Sézary syndrome.
Serum soluble CD48 levels as a prognostic marker in mycosis fungoides and Sézary syndrome.
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血清可溶性 CD48 水平作为蕈样肉芽肿和 S 的预后标志物
DOI：
10.1016/j.jid.2018.03.1519
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发表时间：
2018
影响因子：
6.5
通讯作者：
Sato S.
中科院分区：
文献类型：
--
作者：
Oka T;Miyagaki T;Takahashi N;Nakajima R;Kamijo H;Suga H;Asano Y;Sugaya M;Sato S.
CD48是信号淋巴细胞激活分子家族的一员，在大多数造血细胞上表达（Latchman et al., 1998）。CD48有两种不同的配体，CD2和CD244，后者与CD48结合的亲和力要高得多（Brown et al., 1998）。CD48通过与这些配体的相互作用，在免疫细胞功能和活化中发挥重要作用，如增强t细胞活化、促进抗原提呈细胞粘附、调节细胞毒性t细胞和自然杀伤细胞免疫等，与自身免疫、过敏、感染、癌症等多种疾病有关（McArdel et al., 2016）。除了膜结合形式外，CD48还以可溶性形式存在于人血清和血浆中（Smith et al., 1997），尽管目前尚不清楚可溶性CD48 （sCD48）是如何产生的。血浆sCD48水平在晚期淋巴细胞恶性肿瘤和关节炎患者中首次报道升高（Smith et al., 1997）。最近的一项研究表明，轻度特应性哮喘患者血清sCD48水平升高（Gangwar et al., 2017）。另一方面，还没有关于皮肤疾病患者血清sCD48水平的研究。在这里，我们测量了皮肤t细胞淋巴瘤和特应性皮炎（AD）患者的血清sCD48水平，以研究sCD48水平是否可以作为疾病标志物。患者血清样本来自34蕈样(MF)(阶段IA 9日阶段IB 7阶段活动花絮1,IIB阶段9日阶段iii a 3阶段IVA1 3,和舞台IVA2 2;平均年龄±标准差(SD) = 58.4±16.5年;22岁男性和女性12日),12 Sezary综合征(SS)患者(阶段IVA1 9和阶段IVA2 3;平均年龄±SD = 64.1±14.8年;10 2男性和女性),33 AD患者(温和,n = 11,温和,n = 11日严重,n = 11;平均年龄±SD = 36.8±13.1年;男性21例，女性12例)，健康对照14例（平均年龄±SD= 43.9±11.4岁，男性8例，女性6例）。所有MF/SS患者均根据国际皮肤淋巴瘤学会/欧洲癌症研究和治疗组织的标准进行诊断（Olsen et al., 2007, Willemze et al., 2005）。对于MF患者，临床分期IIB及以上定义为晚期，临床分期I期和IIA期定义为早期。所有AD患者均按照Hanifin和Rajka（1980）的标准入组。AD的疾病严重程度由医师全球评估确定。健康对照者无过敏史、AD史、牛皮癣史或恶性肿瘤史。东京大学的医学伦理委员会批准了所有描述的研究。获得使用血样的书面知情同意。免疫反应性sCD48采用人ELISA试剂盒（中国北京中诺生物有限公司）进行定量。采用Kruskal-Wallis检验分析差异的显著性。相关系数采用Spearman秩相关检验确定。p值小于0.05被认为具有统计学意义。
CD48 is a member of the signaling lymphocyte activation molecule family and is expressed on most hematopoietic cells (Latchman et al., 1998). CD48 has two different ligands, CD2 and CD244, and the latter binds to CD48 with a much higher affinity (Brown et al., 1998). Through interactions with these ligands, CD48 plays important roles in immune cell function and activation, such as enhancing T-cell activation, facilitating adhesion of antigen-presenting cells, and modulating cytotoxic T-cell and natural killer-cell immunity, which are associated with a variety of diseases including autoimmunity, allergy, infection, and cancer (McArdel et al., 2016). In addition to the membrane-bound form, CD48 has also existed in a soluble form in human serum and plasma (Smith et al., 1997), although it is still unknown how soluble CD48 (sCD48) is generated. Plasma sCD48 levels were first reported to be increased in patients with advanced lymphoid malignancies and arthritis (Smith et al., 1997). A recent study showed that serum sCD48 levels were increased in mild atopic asthma (Gangwar et al., 2017). On the other hand, there have been no studies investigating serum sCD48 levels in skin disorders. Here, we measured serum sCD48 levels in patients with cutaneous T-cell lymphoma and atopic dermatitis (AD) to investigate whether sCD48 levels can be a disease marker.Serum samples were obtained from 34 patients with mycosis fungoides (MF)(stage IA 9, stage IB 7, stage IIA 1, stage IIB 9, stage IIIA 3, stage IVA1 3, and stage IVA2 2; mean age±standard deviation [SD]= 58.4±16.5 years; 22 males and 12 females), 12 patients with Sézary syndrome (SS)(stage IVA1 9 and stage IVA2 3; mean age±SD= 64.1±14.8 years; 10 males and 2 females), 33 patients with AD (mild, n= 11; moderate, n= 11, severe, n= 11; mean age±SD= 36.8±13.1 years; 21 males and 12 females), and 14 healthy control individuals (mean age±SD= 43.9±11.4 years; 8 males and 6 females). All patients with MF/SS were given diagnoses according to International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer criteria (Olsen et al., 2007, Willemze et al., 2005). As for patients with MF, clinical stage IIB or greater was defined as advanced stage, and clinical stage I and IIA were defined as early stage. All patients with AD were enrolled according to the criteria of Hanifin and Rajka (1980). The disease severity of AD was determined by Physician Global Assessment. The healthy control individuals had no history of allergy, AD, psoriasis, or malignancies. The medical ethics committee of the University of Tokyo approved all described studies. Written informed consent was obtained to use blood samples. Immunoreactive sCD48 was quantified by human ELISA kits (Sino Biological Inc., Beijing, China). Significance of difference was analyzed with Kruskal-Wallis test. Correlation coefficients were determined by using the Spearman rank correlation test. P-values of less than 0.05 were considered statistically significant.