斑秃的基因组学研究进展

秃及一大类其他自身免疫病和炎性疾病有着强的关联性.易感基因、免疫系统紊乱和外界环境等因素的相互作用决定斑秃的发生.     

斑秃治疗进展

斑秃是一种皮肤科常见的良性、以非瘢痕性脱发为主要表现的疾病,严重影响美观.传统的治疗方法基于局部或系统应用糖皮质激素或米诺地尔等促毛发生长药物.随着对斑秃发病机制研究的不断深入,出现了一些新的尝试性的治疗方法,如免疫调节剂、新型生物制剂、308 nm准分子激光、PUVA 等,由于这些疗法缺乏大规模随机对照试验的证据支持并存在较多不良反应,因此在临床上的应用受到限制,但为以后开发新型治疗药物提供了有益的思路.今后斑秃治疗研究的热点将是针对发病机制的靶向治疗并最大限度减少不良反应.     

斑秃的研究进展

斑秃是一种由T淋巴细胞介导的针对毛囊的器官特异性自身免疫性疾病,正常毛囊的免疫赦免作用的破坏在其发病过程中起着重要作用。精神心理因素可使病情加重或反复。目前通过全基因组关联分析至少发现了8个与斑秃发病有关的基因区域,为更好地认识斑秃的发病机制和寻求新的治疗方法提供了遗传学的理论基础。斑秃的发病机制尚不完全清楚,了解斑秃的流行病学、病因及治疗方法对斑秃的处理有指导意义     

Cell-mediated immunity in alopecia areata

Summary A study of cell-mediated immunity was carried out in a total of 69 subjects with alopecia areata (AA) of the scalp in various phases of its evolution. The blastic responses to mitogens PHA, Con A, and PWM proved significantly reduced, quite independently of the phase of the disease. The total E-rosettes test demonstrated a significant reduction in T-lymphocytes in patients with active AA. On the other hand, no significant differences could be demonstrated between the patients and the controls by means of active E rosette test. The mean values for T and for theophylline-sensitive T-lymphocytes were reduced in patients with active AA. The significance of the results is discussed.     

Efficacy and tolerability of methotrexate in severe childhood alopecia areata

Background Alopecia areata (AA) occurring in childhood is associated with a poorer prognosis than adult AA and may severely affect quality of life. The efficacy of methotrexate (MTX) was reported in adults with AA but there is little information about its use in children. Objectives We aimed to assess the efficacy and safety of MTX in severe childhood AA. Methods We conducted a retrospective study including children with severe AA treated with MTX in the Departments of Paediatric Dermatology in France between November 2005 and December 2009. Results Fourteen children (eight girls and six boys) aged between 8 and 18 years (mean 14·7) were included. AA was present for a mean duration of 5·7 years (range 2 months–11 years 8 months). The treatment was administered once weekly, the mean maximal dose was 18·9 mg weekly (range 15–25) and the mean duration of treatment was 14·2 months (range 1–31). Thirteen children were assessable. Of these 13 children, MTX was considered as successful (regrowth > 50% of hair) for five of them. The remaining eight children were considered treatment failures. No serious side‐effects were reported. Conclusions The efficacy of MTX in children with severe AA is variable. MTX may be considered for severe childhood AA in the absence of alternative effective treatments.     

斑秃的基因组学研究进展

斑秃是由多基因和环境因素相互作用引起的毛囊T细胞介导的自体免疫性疾病,斑秃的易感性及不同表型包括不同的发病年龄、不同的临床类型、反复发作或自行缓解以及对治疗的抵抗或有效由多个基因决定,斑秃为一种多基因复杂性疾病。目前用全基因组扫描方法和候选基因方法发现斑秃患者具有一定的易感染色体,斑秃的多个基因存在核苷酸多态性。HLA—DQB和HLA—DR是斑秃发生的高风险基因,HLA—DRB1＊03,HLA—DRw52a可能是斑秃的保护基因。IL-1及其相关家族基因尤其IL-1受体拈抗剂、PTPN22、MIF等基因与斑秃及一大类其他自身免疫病和炎性疾病有着强的关联性。易感基因、免疫系统紊乱和外界环境等因素的相互作用决定斑秃的发生。     

斑秃的治疗现状

斑秃是一种累及生长期毛囊的免疫相关性疾病.斑秃的治疗主要是依据患者的年龄、疾病的严重程度及持续时间来选择合适的治疗方法,包括糖皮质激素、米诺地尔、免疫疗法、生物制剂及试验性治疗和疾病管理措施等,但至今尚无确切有效的治疗和预防的方法,有些疗法也没有系统的随机、对照试验证据,其治疗方面仍是一大挑战.目前认为,斑秃是一种毛囊免疫赦免破坏的自身免疫性疾病,免疫抑制可控制病情,进一步重建免疫状态成为斑秃治疗的理想观念.     

雄激素性脱发和斑秃患者生活质量及抑郁情况调查分析

目的 调查脱发患者生活质量与抑郁状态及其影响因素,为改善其生活质量采取相应临床对策提供依据.方法 采用皮肤病生活质量指数(DLQI)和流行病学研究中心抑郁量表(CES-D),对雄激素性脱发和斑秃脱发患者237例进行问卷调查,评估其生活质量与抑郁状况,使用方差分析和logistic回归分析其影响因素.结果 237例脱发患者收集到有效答卷218份,218例脱发患者DLQI量表均分为9.1±5.4,总体上脱发对生活质量的影响为中度影响,重度及以上影响者占38.07%.CES-D量表均分为14.8±9.9,有抑郁倾向者占37.61%.DLQI得分和CES-D得分呈正相关(r=0.29,P<0.01).单因素方差分析结果显示,不同年龄、性别、文化程度及就诊次数对DLQI得分差异无统计学意义.多因素logistic回归分析显示,脱发患者发生抑郁倾向的危险因素有:就诊次数(OR=1.81,95%CI:1.21~2.69)和DLQI影响程度(OR=1.08,95%CI:1.03~1.13).结论 脱发不仅影响患者生活质量,而且给患者心理带来负面影响.     

Suppressor cell decrease in alopecia areata

Summary There is considerable evidence to suggest that autoimmunity plays a role in the pathogenesis of alopecia areata. Since it is known that T cells regulate the immune system, a study was undertaken to measure T helper (OKT-4) and T suppressor (OKT-8) cells in the peripheral blood of patients with alopecia areata (both active and stable) and in controls. Total T cells, B cells, immunoglobulins, and autoantibodies were also measured. There was a highly significant decrease in the T-suppressor cell population of patients with alopecia areata (P>0.001). Two of ten patients had microsomal antibodies and three of ten had elevated IgE levels. Other parameters were not significantly different. The decrease in suppressor cells suggests an impairment of the prime negative regulator of the immune system, with loss of tolerance and resultant autoimmunity.     

斑秃发病机制中相关因子的研究进展

斑秃是生长期毛囊自身免疫性疾病,受内源性或外源性因素的刺激诱发.研究显示,在斑秃发病过程中,细胞因子和一些小分子起关键作用.干扰素-γ、白介素类以及肿瘤坏死因子-α是疾病中常见的重要细胞因子.干扰素-γ诱导的单核因子,干扰素诱导蛋白10,B细胞激活因子,HLA抗原以及应激激素在斑秃中起一定作用.概述斑秃病因的复杂性以及潜在的机制,提出可能的治疗方法.

Abstract：

Alopecia areata (AA) is an autoimmune disease affecting the anagen-stage hair follicles, and is triggered by internal or external factors. It has been revealed that cytokines and some small molecules play essential roles in the development of AA. Interferon (IFN)-γ, interleukins and tumor necrosis factor-α are common cytokines involved in the pathogenesis of diseases. Monokine induced by IFN-'γ, IFN-γ inducible protein 10, B cell activating factor, HLA antigens, as well as stress hormones play certain roles in the development of AA. Within the scope of this paper, the authors attempt to summarize the complexity of etiology of, underlying mechanisms of and possible treatment options for AA.     

斑秃患者皮损丝聚蛋白的表达

【摘要】 目的 探讨丝聚蛋白表达水平与斑秃患者特应性素质和疾病严重程度的关系。方法 分析37例斑秃患者的临床资料及实验室资料,取斑秃皮损和正常对照的头皮进行免疫组化染色,用荧光半定量RT-PCR检测22例斑秃皮损和正常对照的头皮丝聚蛋白在蛋白质和信使RNA的表达水平。结果 斑秃皮损丝聚蛋白和其mRNA的表达水平较正常对照明显降低（P < 0.05或0.01）,而且这种降低在脱发面积较大、病程较长和有指甲改变的斑秃患者中更明显,但降低水平与是否伴发特应性疾病无关。斑秃患者伴特应性疾病组与不伴特应性疾病组之间性别、发病年龄、病程、脱发面积、家族史、甲改变、血清IgE和嗜酸粒细胞升高的发生率等方面差异均无统计学意义。结论 斑秃患者其皮损丝聚蛋白及其mRNA的表达水平均降低,提示丝聚蛋白可能参与斑秃的发病,并和疾病的严重程度有关。     

Inmunoterapia con difenciprona en alopecia areata extensa. Experiencia en 104 pacientes

IntroductionAlopecia areata (AA) is a T cell-dependent, organ-specific autoimmune disease. Topical diphencyprone is the treatment of choice in extensive AA.Materials and methodsThis study describes a series of 104 patients with extensive AA treated with topical diphencyprone to assess the efficacy and adverse effects of this drug.ResultsAfter a mean follow-up of 1 year, most patients in our series (87.5%) showed some response to treatment. Among responders, approximately half the patients had a poor response (grade 1-2) and the other half a higher response (grade 3-4). Adverse effects were mostly local and mild and included blistering, exudation, postinflammatory hyperpigmentation and microadenopathies.ConclusionWe conclude that immunotherapy with diphencyprone is easy to implement, effective and well tolerated by patients.     

Receptor site dominance after hair transplantation in alopecia areata

A 32-year-old woman presented with a patchy and ophiasis type of alopecia areata. She reported that at the age of 25 she had undergone plastic surgery for the same hair problem. In the occipital region, partial excision of bald areas and transplantation of punched grafts from unaffected areas of her scalp had been performed, but these grafts completely lost their hair shortly after transplantation. At the age of 30 she had developed, in addition, patchy alopecia areata in other areas of the scalp. The present observation of receptor site dominance of the area affected by alopecia areata suggests that the primary abnormality is situated in the affected tissue, and that the disease is caused by local spreading of a hitherto unknown factor.     

Immunopathological studies on alopecia areata

Summary Anti-endothelial cell antibodies could be removed from circulating lymphocytes by means of acid elution techniques in eight patients with different degrees of alopecia areata. These antibodies were specifically directed against the endothelial cells in the capillary network of the hair bulb, indicating the existence of an antigen, which is unique to these particular endothelial cells. These antibodies do not bind complement in vitro and are species-specific.Circulating ANA (speckled type) were only noticed in case with alopecia areata in spots. A significant decrease in circulating T cells was noticed in six of eight patients with a certain degree of alopecia.Based on a paper presented at the 1st International Congress of Hair Research, Hamburg, March 1979     

神经肽和HPA轴因素在斑秃发病中的作用

斑秃是一种毛囊的自身免疫性疾病,其发病机制中精神应激机制的研究热点集中在两方面:一是对作为大脑-皮肤之间的神经免疫内分泌联系的神经肽类的研究:外部应激因素可通过P物质、降钙素基因相关肽、神经生长因子、肥大细胞、巨噬细胞、γ8T细胞组成相互作用的网络,这些物质组成"脑-毛囊轴",毛囊对这些应激介质高度敏感,应激正是通过这个途径影响毛发生长;二是对皮肤作为外周类似下丘脑-垂体-肾上腺轴功能单位的研究:皮肤具有自己的神经内分泌系统,皮肤及其附属器也能产生同样的系统性应激反应所需要的介质,人类皮肤也可表达促皮质素释放激素.     

斑秃毛囊退行性变及局部炎症细胞浸润的研究进展

斑秃是一种非瘢痕性的炎症性脱发性疾病,病情多能自限,但容易复发。斑秃发病机制不明,组织病理上表现为生长期毛囊周围炎症浸润及毛囊退行性变两个部分。目前研究认为,内外源因素作用于遗传易感人群引起生长期毛囊深层周围炎症细胞浸润,浸润的炎症细胞及细胞因子、神经肽等形成恶性循环,循环结局为毛囊上皮细胞凋亡,大批毛囊同时陕速进入退行期,导致斑秃发生。     

T淋巴细胞亚群与斑秃发病关系的研究

目的:探讨T细胞亚群(CD3 、CD4 、CD8 T)在斑秃发病中所起的作用。方法:用流式细胞仪分别检测斑秃患者PBMC中CD3 、CD4 、CD8 T淋巴细胞的表达水平。结果:重型斑秃、轻型斑秃的CD4 T淋巴细胞表达高于正常对照组,且差异有统计学意义;重型斑秃、轻型斑秃的CD8 T淋巴细胞表达亦高于正常对照组,且差异有统计学意义;CD3 T淋巴细胞表达、CD4 /CD8 比值较正常对照升高,差异无统计学意义。结论:提示了由T淋巴细胞介导的斑秃的发病机理,CD8 和CD4 T淋巴细胞在其发病过程中起到重要作用,两者协同作用导致毛囊受损。     

The genetic epidemiology and autoimmune pathogenesis of alopecia areata

Unlit recently, there was only circumstantial evidence to support the autoimmune and genetic etiology of alopecia areata. The advent of HLA stereotyping and linkage analysis has revealed an increase in specific HLA alleles in patients with alopecia areata and controls. Even more current is the detection of autoantibodies to the hair follicle in the sera from humans with alopecia areata and laboratory animal models of the disease. Recent experiments suggest that there may even be specific HLA class II alleles that play a protective role against the development of alopecia areata. Herein, the circumstantial data and the confirmed linkage data to support a genetic/autoimmune interplay theory of alopecia areata are discussed. The temporal advancements of research in the area of the HLA typing are reviewed for the disease.     

In situ demonstration of T cells in alopecia areata

Summary Local application of alpha-l-fucose on the ear before elicitation of contact allergy to dinitrofluorobenzene (DNFB) in BALB/c mice results in a suppression of the contact allergic response. However, local application of alpha-l-fucose at the sensitization site on the abdominal wall before sensitizing the animals with DNFB had no inhibitory effect on contact allergy. Alpha-l-fucose has been demonstrated to inhibit lymphokine activity in vitro and manifestation of cellular immunity in vivo. Our results suggest that alpha-l-fucose suppresses contact allergy by locally inhibiting the efferent phase of the cellular immune response.