梅花针叩刺联合桃红四物汤加味治疗气滞血瘀型白癜风的临床疗效及对血清免疫球蛋白和自身抗体的影响

摘要 目的：观察气滞血瘀型白癜风经桃红四物汤加味、梅花针叩刺联合治疗后的临床疗效及对血清免疫球蛋白（Ig）和自身抗体的影响。方法：根据随机数字表法将中国中医科学院广安门医院2019年3月~2022年4月期间收治的80例气滞血瘀型白癜风患者分为对照组（常规治疗的基础上结合梅花针叩刺治疗）和观察组（对照组的治疗基础上结合桃红四物汤加味治疗），各为40例。对比两组疗效、中医证候评分、白斑面积、出现黑素细胞时间、白斑的色素积分、血清自身抗体、Ig水平以及不良反应发生率。结果：观察组的临床总有效率为95.00%（38/40），高于对照组的75.00%（30/40）（P<0.05）。观察组治疗3个月后抗甲状腺球蛋白抗体（A-TG）、抗甲状腺过氧化物酶抗体（A-TPO）阳性率低于对照组（P<0.05）。观察组治疗3个月后面色晦暗、肌肤甲错、心烦不安、气郁不舒、失眠多梦评分低于对照组（P<0.05）。观察组治疗3个月后出现黑素细胞时间短于对照组，白斑的色素积分高于对照组，白斑面积小于对照组（P<0.05）。观察组治疗3个月后血清IgA、IgG、IgM高于对照组（P<0.05）。两组不良反应发生率比较无差异（P>0.05）。结论：气滞血瘀型白癜风经桃红四物汤加味联合梅花针叩刺治疗，临床症状得到显著改善，自身抗体阳性率降低，机体免疫力提高，且治疗安全性较高。     

Vaccine-specific local T cell reactivity in immunotherapy-associated vitiligo in melanoma patients

The occurrence of vitiligo in patients with melanoma is especially reported for patients undergoing immunotherapy. While vitiligo in these patients is thought to be related to an immune response directed against melanoma cells, solid evidence is lacking. Here we report local cytotoxic T cell reactivity in three melanoma patients who developed vitiligo, after experimental immunotherapy using dendritic cell vaccinations. Tetramer analysis showed that vaccine-induced T cells recognizing gp100 and tyrosinase are present at the vitiligo lesions. These T cells secrete IFN-γ and IL-2 upon peptide specific stimulation as well as upon recognition of the autologous tumor. We show that functional CD8⁺ T cells specific for melanoma differentiation antigens used in a melanoma immunotherapy trial, do not only invade the tumor, but also the vitiligo lesions. This directly links vitiligo to the immuno-therapeutic intervention and supports the hypothesis that vitiligo is a marker of immunity against melanoma cells. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Vitiligo: Where Do We Stand?

Vitiligo is a puzzling disorder characterized by a disappearance of epidermal and/or follicular melanocytes by unknown mechanisms. This very common disorder involving 1–4% of the world population is thus of great importance for the practicing dermatologist. The cellular and molecular mechanisms leading to the destruction of melanocytes in this disorder have not yet been elucidated, making it of major interest for the cell biologist involved in melanocyte research. Recent advances in this field, due largely to the availability of techniques for culturing normal human melanocytes, opened new perspectives in the understanding of vitiligo. Although vitiligo has long been considered a disorder confined to the skin, there is now good evidence that it also involves the extracutaneous compartment of the “melanocyte organ.” It is also clear that vitiligo is not only a melanocyte disorder, but that it also involves cells, such as keratinocytes and Langerhans cells, found in the epidermis and follicular epithelium. The three prevailing theories of the pathogenesis of vitiligo are the immune hypothesis, the neural hypothesis, and the self-destruct hypothesis. New hypotheses suggest that vitiligo may be due to (1) a deficiency in an unidentified melanocyte growth factor, (2) an intrinsic defect of the structure and function of the rough endoplasmic reticulum in vitiligo melanocytes, (3) abnormalities in a putative melatonin receptor on melanocytes and (4) a breakdown in free radical defense in the epidermis. None of these hypotheses has been demonstrated, and according to the available data, it is likely that the loss of epidermal and follicular melanocytes in vitiligo may be the result of several different pathogenetic mechanisms.     

太原市杏花岭区白癜风患者临床流行病学调查及患病影响因素的Logistic回归分析

摘要 目的：调查太原市杏花岭区白癜风患者临床流行病学情况,并分析患病影响因素。方法：于2020年6月至2021年6月采用多阶段分层随机抽样的方法,抽取太原市杏花岭区辖10个街道符合条件的常住居民进行调查,共抽取1440例,实际完成调查研究1428例,应答率为99.17%。采用我院自行设计的问卷调查表收集资料。根据是否患有白癜风将研究对象分为白癜风组（n=31）和无白癜风组（n=1397）。采用单因素和多因素Logistic回归分析太原市杏花岭区白癜风患者患病影响因素。结果：纳入的1428例居民中,共诊断出31例患有白癜风,患病率为2.17%。31例白癜风患者中,男性占比高于女性,占54.84%;年龄21~40岁区间患病率最高,占29.04%;未婚的白癜风患者偏多,占45.17%;文化程度为初高中的白癜风发生率偏高,占41.94%;职业为学生的白癜风发生率偏高,占32.27%。单因素分析显示：太原市杏花岭区白癜风的患病与白癜风家族史、精神因素、暴晒史、饮酒史、吸烟史、经常接触化学物质、饮食规律、蔬果摄入量、饮食合理、皮肤病史有关（P<0.05）。多因素Logistic回归分析显示：饮酒史、白癜风家族史、皮肤病史、经常接触化学物质、暴晒史、精神因素是白癜风发病的潜在独立危险因素,而饮食合理、蔬果摄入量大、饮食规律则是其保护因素（P<0.05）。结论：太原市杏花岭区白癜风发生率较高,饮酒史、白癜风家族史、皮肤病史、经常接触化学物质、暴晒史、精神因素是白癜风发病的潜在独立危险因素,而饮食合理、蔬果摄入量大、饮食规律则是其保护因素。     

Antioxidant Status in the Blood of Patients With Active Vitiligo

We have previously reported that patients with active vitiligo (AVP) have elevated urinary levels of catecholamine metabolites, such as homovanillic and vanilmandelic acids, irrespective of the form of the disease (acrofacial, segmental, generalized). We have suggested that abnormal release of catecholamines from autonomic nerve endings might play an etiological role in the onset and development of vitiligo through an overproduction of toxic (oxy)radicals in the microenvironment of melanocytes in the affected areas. In the present study we have investigated whether this suggested increase in radicals might be associated with an oxidative stress in the blood of AVP. We have analyzed by gas-chromatography mass-spectrometry, by high pressure liquid chromatography, by spectophotometry plasma levels of vitamin E (Vit E), lipoperoxides (LIP), and polyunsaturated fatty acids of phospholipids (PL-FA), erythrocyte reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in 62 patients affected with different forms of active vitiligo (acrofacial, segmental, generalized) and in 60 age-matched controls. Our results show that blood levels of Vit E, SOD, GSH, GSH-Px activity, LIP and PL-FA in AVP were not significantly different from those of healthy age matched controls, indicating that melanocyte damage in vitiligo is not linked with a generalized oxidative stress.     

毫火针联合补肾活血方对寻常型白癜风患者外周血炎性因子和免疫指标的影响

目的:探讨毫火针联合补肾活血方对寻常型白癜风患者外周血炎性因子和免疫指标的影响。方法:选取2017年3月2019年7月期间我院收治的寻常型白癜风患者75例,根据随机数字表法分为对照组(n=37)和观察组(n=38),对照组予以常规治疗和补肾活血方,观察组在对照组的基础上联合毫火针治疗,比较两组疗效、白癜风皮损面积、炎性因子[白介素-17(IL-17)、白介素-10(IL-10)、白介素-22(IL-22)]和免疫指标[粒细胞-巨噬细胞集落刺激因子(GM-CSF)、CD4⁺CD25⁺Treg]水平,记录两组治疗期间不良反应情况。结果:观察组治疗12周后的临床总有效率高于对照组(P<0.05)。两组白癜风皮损面积均较治疗前缩小,且观察组小于对照组(P<0.05)。两组患者治疗12周后血清IL-17、IL-22、GM-CSF水平降低,且观察组低于对照组(P<0.05);IL-10、CD4⁺CD25⁺Treg比例水平升高,且观察组高于对照组(P<0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论:毫火针联合补肾活血方治疗寻常型白癜风的疗效显著,可有效提高患者的免疫功能,抑制炎性反应,改善患者临床症状,且用药安全性较好。     

308准分子激光联合他克莫司软膏治疗对白癜风患儿血清免疫球蛋白和IL-17、IL-22的影响

目的:探讨308准分子激光联合他克莫司软膏治疗儿童白癜风的疗效及对血清免疫球蛋白和白介素-17(IL-17)、白介素-22(IL-22)的影响。方法:选取2016年2月~2018年7月期间我院收治的127例白癜风患儿,根据随机数字表法将患儿分为对照组(n=63)和研究组(n=64),对照组患儿给予他克莫司软膏治疗,研究组在对照组的基础上给予308准分子激光治疗,比较两组患儿临床疗效、起效时间、免疫球蛋白、IL-17、IL-22水平,观察两组不良反应发生情况。结果:研究组患儿临床总有效率高于对照组,起效时间短于对照组(P<0.05)。两组患儿治疗后免疫球蛋白A(Ig A)、免疫球蛋白G(Ig G)、免疫球蛋白M(Ig M)均下降,且研究组低于对照组(P<0.05)。两组患儿治疗后血清IL-17、IL-22水平均下降,且研究组低于对照组(P<0.05)。两组不良反应发生率对比无统计学差异(P>0.05)。结论:308准分子激光联合他克莫司软膏治疗白癜风患儿疗效确切,可有效改善血清免疫球蛋白和IL-17、IL-22水平,具有一定的临床应用价值。     

CTLA4 and generalized vitiligo: two genetic association studies and a meta‐analysis of published data

Several lines of evidence have implicated the gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) in susceptibility to various autoimmune diseases. However, published studies of genetic association between CTLA4 polymorphisms and vitiligo have yielded conflicting results. Here, we describe two new genetic association studies of CTLA4 single‐nucleotide polymorphisms (SNPs) and generalized vitiligo in two independent Romanian Caucasian (CEU) case‐control cohorts. The first study, of SNPs rs1863800, rs231806, rs231775, rs3087243, rs11571302, rs11571297, and rs10932037, showed no allelic, genotypic, or haplotypic association with generalized vitiligo. The second study, of SNP rs231775, likewise showed no significant association. To enhance statistical power over that of any individual study, we carried out a meta‐analysis that incorporated these two new studies and all other published genetic association studies of CTLA4 SNPs and vitiligo in CEU populations. While there was no association with vitiligo overall, the meta‐analysis showed significant association of SNP rs231775 in that subgroup of vitiligo patients who also had other concomitant autoimmune diseases. Similarly, there was near‐significant association in this same patient subgroup with several other CTLA4 SNPs that are in linkage disequilibrium with rs231775. Our results indicate that the association of CTLA4 with vitiligo is weak, and indeed may be secondary, driven by primary genetic association of CTLA4 with other autoimmune diseases that are epidemiologically associated with vitiligo.     

HSP70iQ435A to subdue autoimmunity and support anti-tumor responses

Developing immunosuppressive therapies for autoimmune diseases comes with a caveat that immunosuppression may promote the risk of developing other conditions or diseases. We have previously shown that biolistic delivery of an expression construct encoding inducible HSP70 (HSP70i) with one amino acid modification in the dendritic cell (DC) activating moiety 435–445 (HSP70i_Q435A) to mouse skin resulted in significant immunosuppressive activity of autoimmune vitiligo, associated with fewer tissue infiltrating T cells. To prepare HSP70i_Q435A as a potential therapeutic for autoimmune vitiligo, in this study we evaluated whether and how biolistic delivery of HSP70i_Q435A in mice affects anti-tumor responses. We found that HSP70i_Q435A in fact supports anti-tumor responses in melanoma-challenged C57BL/6 mice. Biolistic delivery of the HSP70i_Q435A-encoding construct to mice elicited significant anti-HSP70 titers, and anti-HSP70 IgG and IgM antibodies recognize surface-expressed and cytoplasmic HSP70i in human and mouse melanoma cells. A peptide scan revealed that the anti-HSP70 antibodies recognize a specific C-terminal motif within the HSP70i protein. The antibodies elicited surface CD107A expression among mouse NK cells, representative of antibody-mediated cellular cytotoxicity (ADCC), supporting the concept, that HSP70i_Q435A-encoding DNA elicits a humoral response to the stress protein expressed selectively on the surface of melanoma cells. Thus, besides limiting autoimmunity and inflammation, HSP70i_Q435A elicits humoral responses that limit tumor growth and may be used in conjunction with immune checkpoint inhibitors to not only control tumor but to also limit adverse events following tumor immunotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12192-021-01229-x.