Tumour necrosis factor-α antagonists as therapies for vitiligo.
Tumour necrosis factor-α antagonists as therapies for vitiligo.
复制标题
肿瘤坏死因子-α 拮抗剂作为白癜风的治疗方法。
DOI：
10.1111/bjd.14057
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kemp,EH
中科院分区：
文献类型：
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作者：
Kemp,EH
白癜风是一种常见的皮肤疾病，由于表皮黑素细胞的损失。虽然白癜风的病因和发病机制尚未完全了解，但针对黑素细胞的细胞毒性T细胞反应在该疾病的病理生理学中发挥着重要作用。2此外，白癜风患者皮肤内细胞因子的失衡与黑素细胞的破坏有关。3例如，白癜风皮肤中促炎细胞因子肿瘤坏死因子（TNF）-a的表皮水平升高，并且确实与正在进行的色素脱失直接相关。4 TNF-α可激活皮肤中的细胞毒性T细胞，5抑制黑素细胞的增殖，6并导致黑素细胞凋亡。这些发现促使人们研究TNF-α抑制剂作为药物，可以防止白癜风患者的黑素细胞损失，也可以启动色素沉着。在本期BJD中，Webb等8回顾了关于使用抗TNF-α介质（如英夫利昔单抗、依那西普和阿达木单抗）作为白癜风治疗工具的文献。他们的研究结果表明，阻断TNF-α的作用有效地阻止了白癜风的进展，并在几乎所有活动性疾病患者中启动了色素沉着，推测至少部分是由于细胞毒性T细胞介导的黑素细胞破坏的阻止。重要的是，研究人员指出，黑素细胞损失的抑制在评估治疗成功方面与观察实际的色素沉着恢复一样有效，因此得出结论，未来的临床试验将需要有效地评估这两个参数。有趣的是，文献报道了一小部分没有白癜风的患者接受TNF-α拮抗剂阿达木单抗和英夫利昔单抗治疗其他自身免疫性疾病，并发生色素脱失。这篇综述的作者认为，这种现象是由于调节性T细胞（TCLs）的产生和活化减少所致，TCLs通常由TNF-α 9刺激，并抑制细胞毒性T细胞活性。如果皮肤中Treg细胞数量减少，那么对黑素细胞具有细胞毒性的T淋巴细胞可能发挥其作用，导致色素细胞损失。同时进行治疗以将Treg募集到表皮可以克服易感个体的这种逆境。总体而言，发现TNF-α抑制剂对进展性白癜风患者有益。然而，白癜风可以由TNF-α拮抗剂引发的可能性可能会阻碍其作为疾病治疗的更广泛应用。
Vitiligo is a common cutaneous disease resulting from the loss of epidermal melanocytes. 1 Although the aetiology and pathogenesis of vitiligo are not completely understood, cytotoxic T-cell responses against melanocytes clearly play a prominent role in the pathophysiology of the disease. 2 In addition, an imbalance of cytokines within vitiligo-affected skin has been implicated in the destruction of melanocytes. 3 For example, epidermal levels of the proinflammatory cytokine tumour necrosis factor (TNF)-a are increased in vitiligo skin and, indeed, correlate directly with ongoing depigmentation. 4 TNF-a can activate cytotoxic T cells in the skin, 5 inhibit the proliferation of melanocytes6 and also cause melanocytes to apoptose. 7 Such findings have prompted the investigation of TNF-a inhibitors as agents that may prevent melanocyte loss and also initiate repigmentation in patients with vitiligo. In this issue of the BJD, Webb et al. 8 have reviewed the literature pertaining to the use of anti-TNF-a mediators such as infliximab, etanercept and adalimumab as therapeutic tools for vitiligo. Their findings revealed that blocking the action of TNF-a effectively stopped the progression of vitiligo and initiated repigmentation in almost all patients with active disease, presumably at least in part due to the stemming of cytotoxic T-cell-mediated destruction of melanocytes. Importantly, the researchers noted that the arrest of melanocyte loss was as valid in assessing the success of treatment as observing actual repigmentation, concluding that future clinical trials will need to effectively evaluate both parameters. Interestingly, the literature reported a small proportion of patients without vitiligo who were receiving treatment with TNF-a antagonists adalimumab and infliximab for other autoimmune diseases and who developed depigmentation. The authors of the review suggest that this phenomenon results from a decrease in the production and activation of regulatory T cells (Tregs), which are normally stimulated by TNF-a9 and act to supress cytotoxic T-cell activity. 10 If Treg cell numbers are reduced in the skin, then T lymphocytes cytotoxic to melanocytes may exert their effects leading to pigment cell loss. Simultaneous treatment to recruit Tregs to the epidermis may overcome this adversity in susceptible individuals. Overall, inhibitors of TNF-a were found to be beneficial for patients with progressing vitiligo. However, the possibility that vitiligo can be initiated by TNF-a antagonists may thwart their wider use as treatments for the disease.