妊娠类天疱疮研究进展

妊娠类天疱疮(PG)是一种罕见的自身免疫性、表皮下大疱性皮肤病,其发病与遗传、环境和免疫等因素有关。临床表现与妊娠多形疹相似。主要治疗药物包括糖皮质激素、免疫抑制剂、免疫球蛋白等。近年来较多文献报道了生物制剂成功治疗PG的案例。本文就PG的发病机制、临床特征及治疗研究进展进行综述。

妊娠类天疱疮的研究进展

妊娠类天疱疮是一种罕见的、自身免疫性、水疱性、妊娠期特异性皮肤病。其发病与遗传、免疫、内分泌和肿瘤等因素相关。通常发生在妊娠中晚期,临床和病理上类似大疱性类天疱疮。妊娠类天疱疮孕妇所产小于胎龄儿或早产儿的几率增加。临床上需要与妊娠瘙痒性荨麻疹性丘疹及斑块、大疱性类天疱疮等相鉴别。治疗方法主要包括糖皮质激素、静脉注射用免疫球蛋白、免疫抑制剂和利妥昔单抗等。

用免疫印迹与酶联免疫吸附试验诊断妊娠性类天疱疮

OBJECTIVES: To investigate the sensitivity of immunoblotting and enzyme-linked immunosorbent assay (ELISA) to detect autoantibodies to bullous pemphigoid antigen 180 in patients with pemphigoid gestationis and to correlate autoantibody serum levels with disease activity. METHODS: In serum samples obtained from 44 pregnant patients before initiation of therapy and from the same number of healthy blood donors, the autoantibody reactivity was assayed by immunofluorescence microscopy on human skin sections as well as Western blot analysis and 2 different ELISAs by using recombinant forms of the immunodominant domain of BP180. In addition, ELISA reactivity with this autoantigen was assayed in 6 patients during the course of the disease, and its correlation with the clinical disease activity was estimated by applying the Spearman rank correlation test. RESULTS: By indirect immunofluorescence microscopy, complement-fixing autoantibodies to the dermal-epidermal junction were found in 93%of patientssera. By immunoblotting and ELISA, autoantibodies to bullions pemphigoid antigen 180 were detected in 93%and 86.3%of pemphigoid gestationis patients, respectively, but in none of the healthy controls. Serum levels of autoantibodies as detected by ELISA paralleled the patients’disease activity. CONCLUSIONS: Our study shows that immunoblotting and ELISA are sensitive tools for the detection of autoantibodies to bullous pemphigoid antigen 180 in patients with pemphigoid gestationis. In addition, the ELISA is useful to monitor autoantibody serum levels.

妊娠相关性瘙痒

妊娠期瘙痒最常见于妊娠特异性皮肤病（specific dermatoses of pregnancy,SDP）,即由于妊娠期体内新陈代谢、免疫、内分泌的改变,出现妊娠期独有的或更易发生的皮肤病,包括妊娠期肝内胆汁瘀积症、妊娠特应性皮疹、妊娠多形疹、妊娠类天疱疮。此外,系统性疾病、药疹、皮肤肿瘤等也可能是妊娠期皮肤瘙痒的原因。充分认识妊娠期瘙痒性皮肤病有助于明确诊断,合理用药,规避胎儿风险。

妊娠期和哺乳期皮肤病的安全用药

妊娠期和哺乳期均会出现皮肤瘙痒和皮疹等改变，有的皮肤病确与妊娠有关，如妊娠瘙痒症（妊娠期肝内胆汁淤积）、妊娠多形疹（妊娠瘙痒性荨麻疹性丘疹或斑块）、妊娠痒疹、妊娠瘙痒性毛囊炎、疱疹样脓疱病、妊娠类天疱疮、妊娠线状IgM病等，但也不能忽视与妊娠无关的一般皮肤病，如疥疮、丘疹性荨麻疹等．

黏膜天疱疮患者循环性NC16-A特定T细胞的快速效应器功能

Background:Mucous membrane pemphigoid (MMP) is a chronic blistering skin dise ase frequently associated with circul atingautoantibodies directed to a number o f antigens including the NC16A region of BP180. NC16A domain-specific T cells h ave been identified in the blood of individuals with bullous pemphigoid (BP), pe mphigoid gestationis and linear IgA disease, but there are no data investigating the potential role for such T cells in the pathogenesis of MMP. Objectives:To test the hypothesis that NC16A-specific T cells exist in the peripheral blood o f individuals with MMP. Methods:We isolated peripheral blood mononuclear cells from 10 patients with MMP, 17 with BP and 10 healthy controls and examined the i mmunogenicity of overlapping peptides spanning the NC16A domain using interferon (IFN)-γenzyme-linked immunospot assay. Results:Significant IFN-γproductio n was observed in response to the NC16A peptides in two of the patients with MMP and two of the patients with BP but in none of the normal controls. These data suggest that in a minority of individuals with MMP, NC16A domain-specific T cel ls circulate at sufficiently high frequency to be detectable directly ex vivo an d to show rapid effector function. Conclusions:Overall, these findings are the first to examine the potential role for antigen-specific autoreactive T cells i n the pathogenesis of MMP, and confirm that in some individuals the NC16A domain may be an important target antigen.

大疱性类天疱疮和妊娠疱疹患者血清抗BP180NC16A抗体的纯化和鉴定

目的 探讨大疱性类天疱疮（BP）和妊娠疱疹（HG）患者血清抗BP180 NC16A抗体的纯化和鉴定方法.方法 原核表达系统pGEX-2TBP180NC16A表达GST/NC16A融合蛋白,将融合蛋白与谷胱甘肽琼脂糖凝聚微珠进行共价偶联.微珠亲和层析法纯化BP和HG患者血清中抗BP180 NC16A抗体,并用ELISA、免疫荧光、及Western印迹进行鉴定.结果 原核表达系统pGEX-2TBP180NC16A表达37 000GST/NC16A融合蛋白,微珠亲和层析法纯化后得单一抗BP180 NC16A抗体.经ELISA方法定量后确定其含量为2.4 mg/ml；该抗体能与人皮肤基底膜带结合,证明抗体活性；免疫印迹可见单一片段,显示抗体纯度.结论 微珠亲和层析法纯化的BP和HG患者血清中抗BP180 NC16A自身抗体活性高、特异性强.

BP180相关自身免疫性水疱病的研究进展

BP180相关自身免疫性水疱病包括大疱性类天疱疮、扁平苔藓样类天疱疮、线状IgA大疱性皮病、妊娠类天疱疮和瘢痕性类天疱疮。BP180胞外区含有多个自身抗体反应的位点,目前研究显示,BP180上相关自身免疫性水疱病靶位呈现出异质性,并且同一种疾病不同临床表现也与靶位异质性有关,然而异质性机制仍有待于进一步研究和探讨。