血浆疗法治疗大疱性类天疱疮的临床疗效及自身抗体水平变化

目的:通过研究大疱性类天疱疮(bullous pemphigoid, BP)患者的临床资料,提高对大疱性类天疱疮的认识,并初步评价血浆疗法治疗大疱性类天疱疮的临床疗效,并探索其治疗机制。方法:2009年12月—2015年12月我院皮肤科收治的大疱性类天疱疮患者66例,28例患者接受血浆疗法联合糖皮质激素治疗,作为血浆疗法组(PT组),38例患者单纯应用糖皮质激素治疗,作为单纯糖皮质激素治疗组(HT组),比较两组的临床疗效,每组各采集16名患者的血清,以20名健康者血清作为对照,采用酶联免疫吸附(ELISA)法检测治疗前后血清中抗BP180抗体水平的变化以及抗BP180抗体亚型IgG1、IgG4水平的变化。结果:PT组有效率为92.86%,HT组为73.68%,PT组的治疗效果更为显著。两组患者治疗后抗BP180抗体滴度明显下降(P0.01),PT组较HT组下降明显(P0.01),PT组患者治疗后抗体亚型IgG1、IgG4测得的吸光度A值明显下降(P0.05)。结论:血浆疗法治疗大疱性类天疱疮有效,其机制可能与降低抗BP180抗体及抗体亚型IgG1、IgG4的水平有关。     

大剂量静脉注射免疫球蛋白治疗25例重症皮肤病的临床分析

目的 探讨大剂量静脉注射免疫球蛋白(大剂量IVIg)治疗中毒性表皮坏死松解症、药物超敏综合征、结缔组织病、自身免疫性疱病、急性移植物抗宿主病等重症皮肤病的临床疗效和不良反应.方法 应用免疫球蛋白0.4g·kg^-1·d^-1静脉滴注,每个疗程时间均为连续5d,治疗25例重症皮肤病.结果 大剂量IVIg对这25例重症皮肤病疗效各有差异,其中21例重症患者疗效较好,尤其是急性发病的中毒性表皮坏死松解症和药物超敏综合征效果最好;1例成人皮肌炎患者和2例老年大疱性类天疱疮患者未得到缓解,1例急性移植物抗宿主病患者死亡;仅3例患者出现轻微头痛、血压升高等.结论 大剂量IVIg是治疗某些重症免疫性皮肤病的有效手段,对于缩短病程、减少糖皮质激素和免疫抑制剂的用量、预防感染等方面疗效明显.     

BP180NC16a-ELISA对大疱性类天疱疮血清学诊断的评价

目的 评价BP180NC16a-ELISA对大疱性类天疱疮血清学诊断的效能.方法 BP患者42例,对照组42例(其中正常人对照24例,天疱疮18例),在患者用药前采血,比较BP180NC16a-ELISA和盐裂试验免疫荧光(IIF)检测的结果.结果 用BP180NC16a-ELISA检测时,BP患者中有1例呈阴性反应,其敏感性为97.62%;正常人对照组中有1例呈阳性反应,其特异性为97.62%,且BP180NC16a-ELISA法的A值与IIF滴度之间无相关性.结论 BP180NC16a-ELISA在疾病初始阶段是检测血清中抗BP180抗体的有效方法.     

大疱及疱疹性皮肤病

20071924大疱性类天疱疮疾病严重程度与BP180抗体水平关系的研究/冯素英(中国医科院协和医大皮研所),靳培英,林麟…∥中华皮肤科杂志.-2007,40(4).-199~201用BP180NC16a-ELISA分别测定20例住院典型大疱性类天疱疮(BP)患者治疗前、病情缓解、糖皮质激素开始减量时和减量至相当于     

大疱性类天疱疮患者黏膜受累与糖皮质激素控制量的相关性

目的 探讨大疱性类天疱疮(bullous pemphigoid,BP)患者黏膜受累与糖皮质激素控制量的相关性。方法 对1988-2002年103例BP住院患者平均糖皮质激素起始控制量、皮损全部消退时间和糖皮质激素开始减量时间进行回顾性研究,按照患者入院时皮损累及部位分为黏膜受累组和无黏膜受累组。结果 103例患者,黏膜受累组37例占35.9%,无黏膜受累组66例占64.1%,黏膜受累组控制病情所需的糖皮质激素量高于无黏膜受累组(t=3.49,P<0.001),两组患者皮损全部消退时间和糖皮质激素首次减量时间差异无显著性(t=0.82和t=0.41,P>0.05)。结论 BP黏膜损害与糖皮质激素控制量相关。     

大疱性类天疱疮患者血清总IgE与血清自身抗体的关系

目的 分析大疱性类天疱疮患者血清总IgE与抗BP180IgG抗体、抗BP230IgG抗体、抗表皮基底膜IgG抗体滴度(即间接免疫荧光滴度)的关系.方法 收集沈阳市第七人民医院2014年1月-2020年1月大疱性类天疱疮病例,进行回顾性分析,根据抗BP180IgG抗体、抗BP230IgG抗体阳性情况将患者分组,比较组间血...     

天疱疮和大疱性类天疱疮患者外周血滤泡辅助性T细胞水平的研究

目的 探讨滤泡辅助性T细胞（Tfh）在天疱疮和大疱性类天疱疮发病中的作用。 方法 天疱疮和大疱性类天疱疮患者各10例,与天疱疮和大疱性类天疱疮患者年龄、性别相匹配的正常人对照各10例。采用流式细胞仪检测外周血单一核细胞（PBMC）中Tfh水平,采用酶联免疫吸附法（ELISA）检测其血清中白介素21（IL-21）水平,同时检测大疱性类天疱疮患者血清中抗BP180-NC16A抗体滴度,并进行抗体滴度与IL-21、Tfh水平的相关性分析。结果 天疱疮患者组血清中IL-21水平（95.33 ± 33.69 ng/L）显著高于其正常人对照组（54.50 ± 18.13 ng/L）（t = 3.38,P ＜ 0.01）,Tfh水平（12.08% ± 4.74%）亦显著高于其正常人对照组（6.15% ± 1.62%）（t = 3.74,P ＜ 0.01）。大疱性类天疱疮患者组血清中IL-21水平（106.70 ± 44.91 ng/L）显著高于其正常人对照组（55.37 ± 15.89 ng/L）（t = 3.41,P ＜ 0.01）,Tfh水平（11.85% ± 3.14%）亦显著高于其正常人对照组（6.03% ± 1.74%）（t = 5.13,P ＜ 0.01）。大疱性类天疱疮组抗BP180-NC16A抗体滴度与IL-21水平呈正相关（r = 0.77,P ＜ 0.01）,与Tfh水平亦呈正相关（r = 0.67,P ＜ 0.05）。结论 天疱疮和大疱性类天疱疮患者Tfh及其分泌的细胞因子IL-21水平均明显升高,可能在其发病过程中起一定的作用。     

低剂量泼尼松治疗系统性红斑狼疮血小板减少的疗效观察

血小板减少是系统性红斑狼疮(SLE)常见并发症之一,也是SLE预后不良的一个独立危险因素^[1]。临床实践中,我们对血小板≤(20～30)×10⁹/L且伴有出血表现的患者,采用泼尼松≥1mg·kg^-1·d^-1合并长春新碱或静脉注射丙种球蛋白进行短期治疗,待血小板≥(40～50)×10⁹/L且无明显出血表现时改为低剂量泼尼松(≤0.25mg·kg^-1·d^-1)治疗并长期随访,效果显著,而且感染等不良反应少见。为评价这一方案的可行性,对这部分患者的临床资料进行回顾性分析,并与同期采用中剂量泼尼松(≥0.5mg·kg^-1·d^-1)治疗患者的临床资料进行对比。     

大疱性类天疱疮患者血清几种趋化因子的检测

目的 探讨大疱性类天疱疮(BP)患者CC型趋化因子家族中嗜酸粒细胞趋化因子(eotaxin)、调节激活正常T细胞表达和分泌的细胞因子(RANTES)、单核细胞趋化蛋白-l(MCP-1)和巨噬细胞炎症蛋白(MIP-lα)的表达.方法 用双抗体夹心ELISA方法检测28例活动期BP患者与30例正常人对照血清eotaxin、RANTES、MCP-1和MIP-lα水平.结果 BP患者血清eotaxin和MCP-1明显高于正常人,P分别<0.001,0.05.RANTES和MIP-lα水平与正常人比较差异无统计学意义(P均>0.05).结论 BP发病中存在趋化因子的异常,eotaxin和MCP-1可能与BP的发病有关.     

自体外周血纯化造血干细胞移植治疗系统性红斑狼疮

目的 探讨自体外周血纯化造血干细胞移植治疗系统性红斑狼疮(SLE)的疗效和安全性。方法 对9例SLE患者进行自体外周血纯化造血干细胞移植。采集的干细胞的计数为(2.37～9.9)×10⁸/kg。预处理方案是环磷酰胺50 mg·kg^-1·d^-1静脉滴注,连用4 d(造血干细胞回输前2～5d)。抗胸腺球蛋白抗体2.5 mg·kg^-1·d^-1静脉滴注,连用4d。同时碱化和水化尿液,保护心、肝和肾功能。从移植后临床表现、SLE相关的免疫学指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果 9例患者均获得成功植入,外周血白细胞总数>1.0×10>/L的时间为移植后7～15 d,血小板>20×10⁹/L时间为移植后0～21d。所有患者均于移植后面部红斑等临床症状完全消失,大部分患者自身抗体转阴。9例患者均出现轻重不一的血清病样反应,1例出现严重的肾衰和心衰,3例有出血性膀胱炎,1例出现心因性精神障碍,1例发生会阴部念珠菌感染。结论 随访1年结果表明,自体外周血纯化造血干细胞移植治疗SLE的近期疗效显著,且相对安全。     

Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid

Background The 180‐kDa transmembrane hemidesmosomal protein (BPAG2) has been identified as an important autoantigen in bullous pemphigoid (BP). Using the NC16A domain as the antigenic target, a highly sensitive and specific enzyme‐linked immunosorbent assay (ELISA) for the detection of autoantibodies to BP180 was developed. Aim To investigate the correlation of clinical severity and ELISA indices in BP. Methods Antibody titers in the sera from 20 patients were measured using BP180NC16a‐ELISA, and an analysis of the correlation of ELISA indices with disease activity was performed. Serum was obtained from each patient with BP at least three times: before the initiation of treatment, during complete disease control just before the decrease in corticosteroid, and when the dosage of corticosteroid was successfully decreased to half the initial dose. Of the 20 patients, three showed recurrence at a later stage, caused by their decision to stop treatment; serum was obtained at the early stage of recurrence. Results ELISA indices were significantly decreased after successful therapy, although indirect immunofluorescence titers did not always show apparent correlations. Indices measured using BP180NC16a‐ELISA were well correlated with disease activity. Three patients decided to stop taking their medication; subsequently (within 1–2 weeks), blisters recurred, and the levels of antibodies to BP180 increased to close to those before the initiation of treatment. Conclusion BP180 antibody titers showed a closer correlation than indirect immunofluorescence titers to disease activity. The titer of BP180 antibody may be a useful tool for the evaluation of disease activity and for the assessment of the effectiveness of treatments in BP.     

Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid

Background

Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies.

Objective

The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP.

Methods

We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed.

Results

The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not.

Conclusion

BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP.     

天疱疮患者血清细胞因子的检测及其与病情的相关性

目的 研究天疱疮患者血清细胞因子的动态变化及其与病情严重程度的相关性.方法 用双抗体夹心ELISA方法检测31例急性发病期和治疗后缓解的天疱疮患者以及15例正常人对照血清白介素4(IL-4)、白介素10(IL-10)、γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)和可溶性IL-2受体(sIL-2R)水平,并以间接免疫荧光法检测患者血清抗体滴度,同时用烧伤面积九分法记录皮损面积.结果 天疱疮患者急性发病期IL-10水平低于正常人(P<0.05),且与皮损面积呈负相关(r=-0.25,P<0.05);sIL-2R和IFN-γ水平高于正常人(P<0.05),且与皮损面积呈正相关(分别为r=0.60,P<0.05;r=0.41,P<0.05);天疱疮抗体滴度与皮损面积无相关性(P>0.05).结论 天疱疮发病中存在细胞因子的异常,IL-10、sIL-2R和IFN-γ水平与病情严重程度有明显的相关性,其水平的检测可用于监控疾病的严重程度并指导临床治疗.     

大疱性类天疱疮患者外用糖皮质激素治疗抵抗的相关因素分析

目的:依据临床和实验室数据,分析大疱性类天疱疮(BP)患者外用糖皮质激素(简称激素)治疗抵抗的相关因素。方法:收集BP患者64例,其中外用激素治疗有效组(即外用激素治疗4周内,连续3 d,每日新发水疱数<3个,以下简称有效组)22例,外用激素治疗无效组(即外用激素治疗4周内皮损未控制,连续3 d,每日新发水疱数≥3个,以下简称无效组)42例。对2组BP患者的皮损类型进行统计,比较2组患者的大疱性类天疱疮疾病面积指数(BPDAI)评分、外周血中白蛋白浓度和嗜酸性粒细胞(EOS)计数以及外周血中抗BP180和抗BP230 IgG抗体、总IgE、抗BP180和抗BP230 IgE抗体浓度。结果:有效组患者的皮损以单纯水疱为主(68%),无效组则以红斑水疱为主(63%)。无效组患者的BPDAI评分、EOS计数、总IgE、抗BP180 IgG抗体、抗BP230 IgG抗体浓度及抗BP230 IgE抗体浓度均较有效组患者明显增高,差异具有统计学意义(P<0.05);而2组患者白蛋白水平及抗BP180 Ig E抗体浓度无明显差异。结论:除BPDAI评分及特异性IgG水平之外,还可根据BP...     

血清白细胞介素21水平与大疱性类天疱疮无相关性

目的 探讨大疱性类天疱疮（BP）患者血清白细胞介素（IL）21水平与抗BP180抗体、嗜酸性粒细胞（EOS）水平、BP疾病面积指数（BPDAI）的相关性。方法 酶联免疫吸附试验检测31例BP患者和31例健康对照血清IL-21水平,并检测患者血清抗BP180抗体滴度,评估13例患者BPDAI,分析IL-21水平与抗BP180抗体滴度、EOS计数及BPDAI的关系。结果 患者组血清IL-21水平［M（P25 ~ P75）］为255.28（156.19 ~ 361.59） ng/L,健康对照组为150.47（72.4 ~ 268.73） ng/L,两组差异无统计学意义（P = 0.14）。BP患者血清IL-21水平与抗BP180 抗体水平［82.98（26.82 ~ 132.92） U/ml］无统计学相关性（rs＝0.18,P = 0.332）。27例有EOS计数的BP患者中,血清IL-21与全血EOS绝对值无统计学相关性（rs＝0.104,P = 0.606）。13例评估BPDAI的患者中,血清IL-21与BPDAI亦无统计学相关性（rs＝-0.233,P = 0.464）。结论 BP患者IL-21水平与抗BP180抗体、EOS水平、BPDAI均不相关。     

大疱性类天疱疮患者血清中抗BP180抗体水平检测及意义的分析

目的研究23例大疱性类天疱疮(BP)患者血清中抗BP180抗体的表达水平和治疗前后的变化及抗体指数与病情严重程度的相关关系,以探讨抗BP180抗体水平在BP患者的诊断、监测病情变化及治疗中的应用。方法对23例患者通过病理及直接免疫荧光进行诊断,并对患者的病情进行评估,应用酶联免疫吸附试验(ELISA)法检测患者及20例正常人血清中抗BP180抗体的水平,最后通过统计分析判断各指标间的关系及意义。结果23例患者血清经ELISA检测抗BP180抗体阳性18例;治疗后的抗BP180抗体指数(67.94±54.73)较治疗前(74.22±59.06)下降,治疗前与治疗后的差值为3.66±12.71,差异有统计学意义(P<0.05);治疗前后抗BP180抗体指数均与病情评分有相关性(治疗前r=0.417,P<0.05;治疗后r=0.818,P<0.01)。20例正常对照组阳性1例,阴性19例。ELISA检测BP血清抗BP180抗体的灵敏度为78.26%,特异性为95%。结论BP患者血清中抗BP180抗体水平与疾病的严重程度有一定的相关性,有较高的灵敏度和特异性,可作为BP的常规辅助诊断,并用于监测病情变化及指导治疗。     

Herpes gestationis in a mother and newborn: immunoclinical perspectives based on a weekly follow-up of the enzyme-linked immunosorbent assay index of a bullous pemphigoid antigen noncollagenous domain

BACKGROUND: Herpes gestationis (HG) is a rare, autoimmune, bullous disease that occurs during the second or third trimester and usually resolves over weeks or months after delivery. Neonates with HG are rare (estimated at 1 per 100,000 cases). Although anti-180-kDa bullous pemphigoid (BP180) autoantibody and transfer of this autoantibody are known as the cause, to our knowledge, no coordinated analysis of clinical symptoms and anti-BP180 antibody enzyme-linked immunosorbent assay titers has been reported in a mother and neonate with HG. OBSERVATIONS: We describe a 33-year-old woman with HG and her neonate with vesicular erythematous lesions and the weekly follow-up results of the BP180 noncollagenous domain (NC16a) enzyme-linked immunosorbent assay. CONCLUSIONS: Almost the same titer of pathogenic antibody as that in the mother is transferred to the neonate. The plasma elimination half-life of anti-BP180 antibody is approximately 15 days in mother and neonate. An abrupt twin peak increase in the BP180 enzyme-linked immunosorbent assay index from maternal serum was observed just before and after delivery, possibly explaining why HG usually occurs in the last trimester of pregnancy and exacerbates postpartum. Lesions in the neonate resolve without treatment far before pathogenic antibody disappears, suggesting that factors other than anti-BP180 antibodies may be involved in the generation of eruptions. Frequent testing of the BP180 enzyme-linked immunosorbent assay greatly facilitates therapeutic planning.     

Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid

The NC16A domain of the 180-kDa bullous pemphigoid antigen (BP180) is the most immunogenic and, probably, pathogenic region in bullous pemphigoid (BP). In the present study, in order to determine whether serum level of circulating anti-BP180 autoantibodies is a valuable serum marker in BP, the immunoreactivity of sera against the NC16A domain of BP180 was measured using enzyme-linked immunosorbent assay (ELISA) in ten patients with BP. Serum levels of anti-BP180 autoantibodies correlated with the clinical course in BP patients, who received various therapeutic agents. The result suggests that this NC16A-ELISA is a useful method for evaluating the clinical course and efficacy of the therapy in patients with BP.     

Serum levels of IgE anti-BP180 and anti-BP230 autoantibodies in patients with bullous pemphigoid

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the hemidesmosomal proteins, BP180 and BP230. NC16A, a non-collagenous stretch of the BP180 ectodomain is the primary target of pathogenic IgG antibodies. Whereas IgG anti-BP180 autoantibodies play a primary role in the pathogenesis, there is a growing number of data regarding the potential pathogenic roles of IgE class autoantibodies in BP. OBJECTIVES: To examine the levels of IgG and IgE autoantibodies against BP180 and BP230, and to investigate mutual association and clinical relevance. METHODS: Sera obtained from 67BP patients and 36 healthy donors were subjected to ELISA assays to measure serum IgG and IgE levels of anti-BP180 and anti-BP230 antibodies. RESULTS: IgG anti-BP180 antibodies were positive in 63 (94%) of 67BP patients. IgG anti-BP230, IgE anti-BP180, and IgE anti-BP230 antibodies were found in 48 (72%), 20 (30%) and 45 (67%), respectively. IgG anti-BP180 levels were correlated with the affected areas. IgG anti-BP230 antibodies tended to increase in proportion to elongation of disease duration. IgE anti-BP230 levels showed a strong association with local eosinophil accumulation, while the levels were reversely related with the affected areas in BP. CONCLUSIONS: IgE autoantibodies to BP180 and BP230 are detected at high frequencies in BP. IgE anti-BP230 antibodies may have a role in attracting eosinophils to the skin lesions.