人类白细胞抗原与自身免疫性皮肤病的研究进展

人类白细胞抗原(HLA)是目前已知的人体最复杂的基因体系,具有高度的多态性和较强的同源性.近年来,随着分子生物学技术的发展及其在HLA研究中的应用,HLA的研究推动了HLA与疾病关联的分子机理研究,文章就HLA基因及分子结构、HLA的功能、HLA等位基因的多态性及其HLA与自身免疫性皮肤病的联系做一简要综述.     

药疹与人类白细胞抗原相关性研究进展

近来研究提示人类白细胞抗原等位基因是药物超敏反应的主要易感基因,与后者的发生有很强的遗传相关性.这种相关性具有药物特异性和种族特异性,表明在药物超敏反应的发生机制中,人类白细胞抗原分子起直接的作用.因此,对这些具有高度敏感性和特异性标记分子进行检测,可以鉴别个体发生药疹的风险.     

人类白细胞抗原与银屑病相关性研究进展

关于银屑病遗传病因学的研究越来越多,人类白细胞抗原基因是其中之一.银屑病与人类白细胞抗原基因的相关性研究提示,银屑病的易感基因或保护基因可能位于人类白细胞抗原基因区内,也可能与人类白细胞抗原单倍型相连锁形成扩展单倍型,这种相关性在不同的种族、地域存在明显差异.目前在中国汉族人群中尚未进行银屑病大样本量人类白细胞抗原基因区域的遗传学研究,今后可以此作为研究方向,以探索中国人群银屑病与人类白细胞抗原基因区域的关联,揭示银屑病病因及发病机制、促进临床治疗,推动银屑病精准医疗的发展.     

人类白细胞抗原-G在皮肤恶性黑素瘤中表达的研究

目的:检测人类白细胞抗原-G(HLA-G)在原发性皮肤恶性黑素瘤(CMM)中的表达情况.方法:以免疫组化法检测35例原发性CMM、22例痣细胞痣HLA-G及Bcl-2的表达,并结合临床及组织病理学进行分析.结果:在CMM中HLA-G蛋白的阳性表达率显著高于痣细胞痣(P=0.029).HLA-G蛋白表达与CMM炎细胞浸润、Bcl-2蛋白表达显著相关(P值分别为0.032,0.008).CMM中HLA-G表达与临床分期、肿瘤厚度、溃疡及生长模式等预后变量无显著相关性.结论:CMM中HLA-G表达上调,可能参与肿瘤的发生及发展.     

白细胞介素-23/白细胞介素-17轴与自身免疫性皮肤病的研究进展

白细胞介素（IL）-23/IL-17轴是近年来新发现的炎性通路,主要依靠IL-23介导Th17效应细胞,产生IL-17等细胞因子,引起炎性反应及异常免疫,参与多种炎症及自身免疫性疾病.随着医学研究的不断进步,人们对IL-23/IL-17轴及其相关细胞、细胞因子,如Th17细胞、IL-23及IL-17等有了更加清晰的认识,并对其作用及机制有了进一步的了解.在越来越多的自身免疫性皮肤病中发现了此轴的参与.重点阐述了此轴在4种常见结缔组织病、寻常型天疱疮及坏疽性脓皮病中发挥的不同作用,针对此轴的治疗可能为这些自身免疫性皮肤病提供新的治疗靶向.     

天疱疮抗原研究进展

天疱疮是一类以患者体内产生针对自身表皮角质形成细胞的特异性抗体IgG，并与角质形成细胞结合造成细胞间黏附的丧失，产生棘刺松解为特征自身免疫性皮肤病，临床上主要表现为皮肤黏膜的松弛性水疱大疱，但其确切的发病机制尚不清楚。主要综述天疱疮抗原的结构、致病机制以及在诊断治疗中的应用3个方面。     

血清可溶性人类白细胞抗原G、白介素-17水平预测先兆流产患者保胎结局的研究

目的 分析血清可溶性人类白细胞抗原G(sHLA-G)、白介素-17(IL-17)水平预测先兆流产患者保胎结局的价值。方法 选取2018年1月至2020年6月在海南省中医院接受保胎治疗的90例先兆流产患者作为研究对象,于治疗10d时根据保胎结局分为成功组(n=71)与失败组(n=19)。统计患者相关资料,分析治疗前血清sHLA-G、IL-17水平预测先兆流产患者保胎结局的价值。结果 90例患者中保胎失败19例,占21.11%;失败组与成功组血清sHLA-G、IL-17、孕酮(P)水平比较,差异具有统计学意义(P<0.05);受试者工作特征(ROC)曲线显示,先兆流产患者保胎治疗前血清sHLA-G、IL-17水平预测保胎失败风险的曲线下面积(AUC)均>0.80,均有较理想的预测价值,且联合预测价值最高。结论 保胎治疗前血清sHLA-G低表达、IL-17过表达可能提示先兆流产患者保胎失败风险高。     

ERAP1基因与银屑病相关性研究进展

银屑病是一种常见的慢性炎症性皮肤病,其发病机制复杂,与遗传、环境、免疫、内分泌等有关.其遗传因素中,除了与银屑病显著相关的人类白细胞抗原(HLA)-C以外,内质网氨基肽酶(ERAP)1基因与银屑病的相关性被国内外研究多次报道,本文就ERAP1基因与银屑病的相关性及ERAP1与HLA-C的关系做一综述.     

银屑病与超抗原相关性的研究进展

临床可见产生超抗原毒素的金黄色葡萄球菌，化脓性链球菌的皮肤或咽部感染与银屑病发病及症状加重有关，细菌超抗原能选择性激少激活表达特异Ｔ细胞受体ＶβＴ细胞，并使之增殖，诱导细胞因子释放，银屑病皮损中Ｖβ２，Ｖβ５．１Ｔ细胞增多，可能与细菌超抗原金葡菌系毒素Ｂ，胃蛋白酶纯化的Ｍ５，链球菌致热性外毒素Ａ，Ｃ有关，其中链球菌Ｍ与５０ｋＤ角蛋白间存在结构同源性和免疫交叉反应，推测细菌超抗原有Ｔ细胞水平操作可能     

银屑病与超抗原相关性的研究进展

临床可见产生超抗原性毒素的金黄色葡萄球菌、化脓性链球菌的皮肤或咽部感染与银屑病发病及症状加重有关。细菌超抗原能选择性激活表达特异T细胞受体VβT细胞,并使之增殖,诱导细胞因子释放,银屑病皮损中Vβ2~+、Vβ5.1~+T细胞增多,可能与细菌超抗原金葡菌肠毒素B、胃蛋白酶纯化的M5、链球菌致热性外毒素A、C有关;其中链球菌M蛋白与50kD角蛋白间存在结构同源性和免疫交叉反应性。推测细菌超抗原在T细胞水平操作可能在银屑病的发病机理中起作用。     

Linear IgA Bullous Dermatosis of Childhood with Autoantibodies to a 230 kDa Epidermal Antigen

Abstract: Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal disease defined on the basis of direct immunofluorescence findings. However, more recent techniques used to study bullous dermatoses suggest that LABD may be heterogeneous. A patient with LABD of childhood (chronic benign disease of childhood, CBDC) was studied by indirect immunofluorescence on salt-split skin and by Western blot in an attempt to characterize the involved autoantigen. This young girl's periorificial (mouth, genitalia), erythematovesicular lesions were diagnosed initially as herpes simplex. Histologic examination revealed eosinophilic spongiosis, suggesting the diagnosis of an autoimmune blistering disease. Direct immunofluorescence showed an exclusive linear IgA deposit at the dermoepidermal junction. Indirect immunofluorescence revealed circulating IgA autoantibodies that reacted with the epidermal side of saltsplit skin; these reacted by Western blot with a 230 kDa epidermal antigen, as in bullous pemphigoid. This case, fulfilling the diagnostic clinical and direct immunofluorescence criteria for LABD/CBDC, seems to represent IgA bullous pemphigoid. It further underscores the nosologic heterogeneity of LABD, which probably includes, apart from bullous pemphigoid, epidermolysis bullosa acquisita and cicatricial pemphigoid.     

北方汉族银屑病家系HLA基因复合体相关研究

目的研究与中国北方汉族银屑病存在基因易感性的HLAⅠ类基因的分布,并分析与银屑病相关的HLA易感单倍型。方法将核心家系成员分为银屑病患者组(27例)和对照组(9例),应用序列特异性引物-聚合酶链反应扩增HLAⅠ类等位基因。HLA各位点等位基因频率以及基因型频率分布采用直接计数法计算,并做Hardy-Weinberg吻合度检验。两组间的等位基因频率的比较采用四格表x~2检验,HLA各位点间连锁不平衡关系应用连锁不平衡参数计算法。结果在两组受检者中,发现HLA-B*37、HLA-Cw*0602在患者中分布频率高于对照组,是该病的致病基因,HLA-B*48在患者组中分布频率低于对照组,是该病的保护基因。发现在银屑病患者组中有显著性连锁不平衡的HLA单倍型9条。结论证实了HLA基因复合体与银屑病之间存在密切关联。     

Linear IgA Bullous Dermatosis with Circulating IgG Autoantibodies to the 230 kD Epidermal Antigen

The patient was a 54-year-old woman with wide-spread bullous lesions on her trunk and oral mucosa. Histologic examination revealed a subepidermal blister with infiltration of neutrophils and eosinophils. Direct immunofluorescence showed an exclusively IgA deposition at the basement membrane zone (BMZ). Indirect immunofluorescence showed that the blister fluid, but not the serum, contained IgG antibodies against the BMZ antigen on the epidermal side of salt-split skin. Using immunoblot analysis with normal human epidermal extracts, both serum and blister fluid reacted with the 230 kD epidermal antigen. Using colloidal gold and direct immunoelectron microscopy, IgA deposition was detected in the lamina lucida. Clinically, the skin lesions responded well to dapsone. We diagnosed this case as linear IgA bullous dermatosis (LABD) with IgG class circulating autoantibodies against the epidermal 230 kD antigen. These antibodies were considered to be secondary to the damage to the epidermal basal keratinocyte in this case.     

牛角角蛋白与人角质层抗原检测抗角质层抗体的比较研究

本文采用生物素———亲和素酶联免疫吸附试验 (BA—ELISA) ,以牛角角蛋白和人角质层为抗原检测了 32名正常人和 5 0名银屑病患者血清中抗角质层抗体 (AcAs)的滴度。虽然以牛角角蛋白作抗原测得血清中AcAs的滴度低于以人角质层作抗原者 (p <0 0 1) ,但两者的滴度存在着正相关及直线回归关系 ,相关系数 (r)颇高 ,正常人组间 (r=0 94,∧Y=0 33+0 73x ,p <0 0 1) ;病人组间 (r =0 89;∧Y =0 13 +1 0 8x ,p <0 0 1)。鉴于用牛角角蛋白作抗原 ,可以避免细菌和真菌污染对实验的影响 ,能真实地反映出AcAs的滴度 ,故作为人角质层抗原的代替物是可行的     

Dermatosis and depressive symptoms

BACKGROUND: Dermatological diseases modify and impair patients' self-image and can result in considerable psychological suffering. The purpose of this study was to determine the prevalence of depressive symptoms in patients consulting for dermatological diseases. PATIENTS AND METHODS: A prospective study was carried out on 5 successive days at the dermatology department of the Saint-Louis Hospital in Paris. A questionnaire designed to assess depressive symptoms, the CES-D, was given to all patients consulting throughout the study period. This self-assessment scale for depression was devised by the National Institute of Mental Health and has been validated over more than 20 years by means of hundreds of large-scale epidemiological studies in both general and selected patient populations. RESULTS: On completion of the 5-day study, 879 questionnaires had been collected. The sex-ratio was 53.4% women to 46.6% men. The prevalence of depressive symptoms as evaluated by the questionnaire was 23.6% for a total of 774 evaluable dossiers. Patients consulting without an appointment (n = 172) represented 22% of study subjects versus 78% attending a scheduled visit (n = 602). Depressive symptoms were found in 31.4% of patients consulting without an appointment versus 21.4% of patients with an appointment (p<0.01). Male patients consulting without an appointment constituted the most fragile group, with depressive symptoms being seen in 38.8% of this population. DISCUSSION: The prevalence of depressive symptoms among patients seen at a hospital dermatology department was 23.6% in this study. This figure was significantly higher among patients consulting without an appointment, and among men in particular. It was equal to or higher than that seen among patients considered as having more incapacitating or painful conditions as assessed using the same questionnaire. The incidence of concomitant depression should prompt dermatologists to investigate for its existence and to take appropriate therapeutic measures in order to reduce the mental suffering of their patients.     

皮肤病与嗜血细胞综合征

嗜血细胞综合征是由于机体免疫功能紊乱,引起单核巨噬细胞系统反应性增生,损害、浸润器官组织,并释放大量细胞因子,造成机体脏器功能损伤的一种综合征。该文就嗜血细胞综合征病因、分型及诊断标准以及伴发的常见皮肤病的诊治等方面的认识现状作一介绍。