抗桥粒芯蛋白抗体对天疱疮的临床诊断价值

目的研究天疱疮患者血清中抗桥粒芯蛋白(desmoglein,Dsg)1和抗Dsg3抗体水平在天疱疮的临床诊断价值。方法采用酶联免疫吸附试验(ELISA)测定62例天疱疮患者血清中抗Dsg1和抗Dsg3抗体水平;间接免疫荧光法(IIF)测定天疱疮抗体Ig G水平。结果 62例天疱疮患者中抗Dsg1抗体或抗Dsg3抗体任一阳性共50例,阳性率80.65%,与间接免疫荧光法(IIF)相比两种方法差异无统计学意义(P0.05)。因此抗Dsg抗体具有和IIF一样的临床诊断价值。34例寻常型天疱疮(PV)中抗Dsg3抗体阳性或抗Dsg1和抗Dsg3抗体均阳的28例,阳性率82.35%;24例落叶型天疱疮(PF)中抗Dsg1抗体阳性的为20例,阳性率83.33%。可见抗Dsg3抗体是PV的鉴别诊断指标,抗Dsg1抗体是PF的鉴别诊断指标。此外,通过对治疗前后抗Dsg1抗和Dsg3抗体的滴度水平的检测发现,抗Dsg1和抗Dsg3抗体还可作为天疱疮治疗监测的指标。结论采用ELISA方法测定天疱疮患者外周血抗Dsg1抗体和抗Dsg3抗体,方法简便,对患者创伤小,有一定的诊断和鉴别诊断价值。另外,抗Dsg1抗体和抗Dsg3抗体还可作为监测天疱疮治疗效果的指标。     

血清抗桥粒芯蛋白1和3抗体在天疱疮临床诊断中的意义

目的探讨血清抗桥粒芯蛋白(desmoglein,Dsg)1抗体和抗Dsg3抗体检测在天疱疮诊断中的临床意义。方法用酶联免疫吸附试验(ELISA)检测拟诊为天疱疮的113例患者血清中的抗Dsg1抗体和抗Dsg3抗体,同时行皮损组织病理以及直接免疫荧光和间接免疫荧光检查。结果 77例(68.14%)患者经组织病理、直接免疫荧光和间接免疫荧光检查确诊为天疱疮,其中Dsg1抗体阳性71例,阳性率62.83%,敏感度为92.21%,特异度100%;Dsg3抗体阳性45例,阳性率39.82%,敏感度58.44%,特异度100%;二者均阳性39例(34.51%)。其余36例(31.86%)患者经组织病理、直接免疫荧光和间接免疫荧光检查确诊为其他大疱性皮肤病,Dsg1抗体和Dsg3抗体均为阴性。结论 ELISA方法测定外周血抗Dsg1抗体和抗Dsg3抗体具有较高的敏感度和特异度,方法简便,对患者创伤小,对天疱疮临床诊断和鉴别诊断具有重要参考价值。     

天疱疮患者病情与抗桥粒芯蛋白抗体水平的相关性研究

目的:研究天疱疮患者血清中抗桥粒芯蛋白(desmoglein,Dsg)1和抗Dsg3抗体水平与其皮肤、口腔黏膜损害严重程度的相关性,同时对间接免疫荧光(IIF)检测的天疱疮抗体滴度与治疗中使用皮质类固醇控制剂量的相关性进行分析。方法:采用酶联免疫吸附试验(ELISA)试剂盒测定55例天疱疮患者血清中抗Dsg1和抗Dsg3抗体水平。结果:抗Dsg1抗体水平与患者皮肤损害严重程度有显著相关性(P<0.01),抗Dsg3抗体水平与口腔黏膜损害严重程度有显著相关性(P<0.01)。天疱疮患者血清IIF滴度与抗Dsg1抗体水平相关(P<0.01),寻常型天疱疮患者IIF滴度与抗Dsg1和抗Dsg3抗体水平均有相关性(P分别<0.01和<0.05)。寻常型天疱疮患者皮质类固醇控制剂量与抗Dsg1抗体水平和IIF滴度显著相关(P<0.05)。结论:ELISA方法检测天疱疮患者抗Dsg1和抗Dsg3抗体对天疱疮的临床诊断、分型、衡量口腔黏膜和皮肤损害严重程度具有一定意义。     

ELISA技术检测寻常型天疱疮桥粒芯蛋白3抗体水平研究

目的:评价酶联免疫吸附试验(ELISA)检测抗桥粒芯蛋白(desmoglein,Dsg)3抗体在寻常型天疱疮(PV)诊断中的意义.方法:对来自不同中心的106例PV患者和106例对照人群血清标本编盲后,进行ELISA检测抗Dsg3自身抗体和间接免疫荧光(IIF)法检测血清天疱疮自身抗体.结果:ELISA法检测Dsg3抗体敏感度为77.4%,特异性为94.3%;IIF法检测抗体敏感度为79.2%,特异性为94.3%.两组间的差异无统计学意义.结论:ELISA方法检测Dsg3抗体对于寻常型天疱疮的诊断是一种较好的辅助方法.     

首次命名淀粉样变型类天疱疮并附一例报道

本文首次提出淀粉样变型类天疱疮的概念，并报道一例。患者中年女性，躯干、四肢苔藓样皮疹伴瘙痒17年，无水疱。组织病理示：真皮乳头大量嗜酸性无定形物质沉积，结晶紫染色：阳性；DIF：真皮乳头及基底膜IgG、IgM颗粒状沉积，C3、IgA阴性；IIF：类天疱疮循环抗体IgG 1∶320阳性。人皮肤盐裂IIF：循环抗体IgG表皮侧阳性；抗BP180抗体0 U/mL，抗BP230抗体169.2 U/mL。     

伴发Castleman病和阻塞性支气管炎的落叶天疱疮型副肿瘤性天疱疮

30岁的男性，首先表现为严重的口唇和口腔黏膜的糜烂，随之头面部、前胸后背出现落叶型天疱疮样的皮疹。皮肤病理表现为表皮上层的棘层松解、散在坏死角质形成细胞、基底细胞水肿和真皮浅层淋巴细胞浸润。大鼠膀胱上皮为底物的间接免疫荧光显示IgG和C3沉积于棘细胞间。Westem blotting显示190-和210-kDa抗原阳性。用重组的Dsg1和13sg3包被的ELISA试剂盒检测显示患者血清中存在抗Dsg1抗体，而没有抗Dsg3抗体。患者的临床、病理和免疫学检查结果符合落叶天疱疮型的副肿瘤天疱疮。患者的后腹膜发现1混合型的Castleman病，手术将其切除后，皮损逐渐好转，但出现了阻塞性支气管炎的症状。     

酶联免疫吸附试验检测血清天疱疮抗体的评价

目的评价酶联免疫吸附试验(ELISA)用于天疱疮血清学诊断的意义。方法用ELISA法检测49例天疱疮患者和36例非天疱疮对照者血清,同时以间接免疫荧光法(IIF)检测患者血清抗桥粒芯糖蛋白(Dsg)抗体滴度,比较两者的检测结果。结果27例寻常型天疱疮(PV)、14例落叶型天疱疮(PF)和6例非天疱疮大疱性疾病患者Dsg1ELISA呈阳性,27例PV、1例PF及1例非天疱疮大疱性疾病患者Dsg3ELISA呈阳性。Dsg1ELISA的敏感性和特异性分别是81.25%和88.89%,Dsg3ELISA的敏感性和特异性分别是81.82%和97.22%。与IIF相比,两者检测结果差异有显著性(χ2=4.31,P<0.05)。结论ELISA是一种简便、敏感和特异性高的天疱疮血清学诊断方法,并能辅助鉴别PV和PF。     

天疱疮282例和类天疱疮366例回顾性研究

目的 探讨天疱疮和类天疱疮诊断与治疗特点.方法 对2003-2007年天疱疮和类天疱疮648例患者的临床资料进行同顾性分析.结果 天疱疮平均发病年龄低于类天疱疮(P＜0.001),直接免疫荧光(DIF)确诊的175例天疱疮患者中IgG100%阳性,C3 92.0%阳性;类天疱疮223例患者中C399.1%阳性,IgG 51.12%阳性.两种大疱性疾病的诊断中,①天疱疮患者的临床诊断、病理检查与DIF三者一致率为68.8%.病理检查、DIF两者一致率为80.7%.②类天疱疮患者的临床诊断、病珲检查与DIF三者一致率为62.8%.病理检查、DIF两者一致率为78.1%.糖皮质激素是治疗两种疾病的主要手段,泼尼松(0.5～1.5)mg·kg-1·d-1可控制大部分患者病情.结论 临床和病理无法确诊的大疱疮和类天疱疮病例,DIF可以作为诊断该病的重要方法.在基层医院,临床怀疑天疱疮,DIF可主要检查IgG、C3,怀疑类天疱疮,可主要检查C3.     

妊娠性类天疱疮

报告1例妊娠性类天疱疮。患者女,30岁。因周身红斑伴瘙痒1个月余,加重伴水疱和灼痛6 d入院。皮肤科检查:周身可见水肿性红斑,其上密集大小不等的厚壁水疱,尼氏征阴性。抗核抗体(ANA)、抗双链(ds)-DNA抗体、抗桥粒芯糖蛋白(Dsg)1抗体、抗Dsg3抗体、抗BP180抗体及抗BP230抗体均阴性。直接免疫荧光(DIF)示基膜带IgG呈线状沉积,IgA、IgM及C3阴性。皮损组织病理检查:表皮下水疱形成,真皮血管周围及间质可见嗜酸性粒细胞和淋巴细胞等浸润。诊断:妊娠性类天疱疮;晚期妊娠33~(+1)周,孕1产0左枕前位(G1P0 LOA)。剖宫早产活婴后,予甲泼尼龙联合静脉注射用人免疫球蛋白(IVIG)冲击治疗。     

大疱及疱疹性皮肤病

20110915血清抗Dsg1特异性抗体水平变化与落叶型天疱疮病情的关系/王佩茹(北大一院皮科),钟珊,陈喜雪…∥中国皮肤性病学杂志.-2010,24(12).-1088~1091检测8例落叶型天疱疮(PF)患者不同时期病情变化及相应时间点血清中特异性抗体的间接免疫荧光(IIF)滴度和Dsg1-ELISA指数,并对结果进行分析。结果:7例(87.5%)患者病情评分与Dsg1-ELISA指数有     

Immunofluorescence Study of Pemphigus from North India

Both serum studies by indirect immunofluorescence (IIF) tests and skin biopsy examination by direct immunofluorescence (DIF) were performed on 22 cases of pemphigus with clinically active lesions. Twenty cases had pemphigus vulgaris and two, pemphigus foliaceus. The majority of cases (70%) were between 21 and 60 years old; the mean age was 39.5 ± 12.7 years. There was no sex predilection. DIF showed the positive fluorescence of intercellular cement substance (ICS) of the epidermis in all 22 cases (100%). IgG was positive in 77.27%, followed sequentially by C3C (50%), IgA (45.45%), and IgM (36.36%). Six cases (27.27%) also showed granular immunoglobulin and/or complement deposits at the dermoepidermal junction. IIF detected serum antiepithelial antibodies in 18 cases (81.81%) using human esophagus as substrate. Most of these cases (88.88%) showed IgG type of antibodies; the other 11.11% exhibited IgA and IgM in low concentrations. 1+ titer positivity was observed in 15 cases. This study demonstrates the value of DIF for a definitive diagnosis of pemphigus. However, it is also important to appreciate that immunofluorescence is not a substitute for histopathology, but rather complementary to it.     

天疱疮患者桥粒芯糖蛋白抗体水平和疾病活动度关系及变化规律分析

目的 研究56例天疱疮患者疾病严重程度和桥粒芯糖蛋白1（Dsg1）和桥粒芯糖蛋白3（Dsg3）酶联免疫吸附试验（ELISA）指数之间的关系,探讨Dsg ELISA指数在不同型别天疱疮中转归的规律。 方法 用ELISA测定36例寻常型天疱疮和20例落叶型天疱疮患者治疗前、病情缓解且糖皮质激素开始减量时、糖皮质激素减量至相当于初始量1/2时、维持治疗开始时以及随诊2年时体内Dsg1和Dsg3 ELISA指数。 结果 Dsg ELISA指数与天疱疮疾病活动度相关,在疾病缓解时,Dsg ELISA指数下降,与治疗前差异均有统计学意义（P < 0.01）。在患者病情稳定使用维持量糖皮质激素、疗程到2年时,落叶型天疱疮中10例（50%）、寻常型天疱疮中7例（19.4%）Dsg1 ELISA指数出现阴性,只有1例（2.7%）寻常型天疱疮患者Dsg3 ELISA指数阴性。 结论 Dsg ELISA指数和天疱疮患者疾病严重程度相关,可能是一种评估病情的有用指标,可对治疗的有效性作出评价。     

天疱疮抗体致棘刺松解量化研究

观察1例寻常型天疱疮不同浓度天疱疮抗体（Pab)致表皮棘刺松解的作用，及对组织尿激酶型纤溶酶原（uPA)表达的影响。结果提示间接免疫荧光（IIF）检出Pab量接近Pab致棘刺松解量，IIF阴性可作为病情缓解的可靠指标，而直接免疫荧光（DIF）更适于作为活动性天疱疮的诊断指标。     

A sensitive and restricted enzyme-linked immunosorbent assay for detecting a heterogeneous antibody population in serum from people suffering from a new variant of endemic pemphigus

We recently described a new variant of endemic pemphigus foliaceus (EPF) in El Bagre, Colombia, that resembles Senear-Usher syndrome and identified autoantibodies to desmoglein 1 (Dsg1), as well as to multiple known and unknown antigens including plectins, in the serum of these patients. Here, we developed a cost-effective ELISA assay capable of detecting the heterogeneous antibody population observed in these EPF patients, and useful for serum epidemiological studies. A protein extract obtained from trypsin-digested fresh bovine skin and further purified on a concanavalin A matrix was used as antigen. This extract contains an important conformational epitope (a 45 kDa tryptic fragment of the Dsg1 ectodomain), which is recognized by antibodies in serum from patients with all varieties of pemphigus foliaceus (PF), and from half of those with pemphigus vulgaris with active clinical disease. The cut-off and threshold values were normalized using human serum obtained from both endemic and non-endemic areas for PF. The efficiency of this ELISA was tested using 600 serum samples from controls and patients diagnosed with EPF, non-endemic PF and other bullous diseases. The overall sensitivity and specificity of the assay were determined to be 95% and 72%, respectively, with reproducibilities of 98% (intraassay) and 95% (interassay). Comparing the ELISA with other tests to detect EPF autoantibodies, this ELISA was the most sensitive, followed by direct immunofluorescence (DIF), indirect immunofluorescence using anti-IgG4 monoclonal antibodies and immunoprecipitation (IP), respectively. The most specific assay was IP, followed by DIF. Immunoblotting to Dsg1 exhibited both poor sensitivity and poor specificity, although plectins were well visualized. We conclude that this ELISA is an excellent tool for field serological studies, allowing testing of multiple serum samples simultaneously and for detecting, with appropriate restriction and sensitivity, the heterogeneous antibody population seen in patients with this variant of EPF. Finally, autoantibody serum levels obtained with this ELISA correlated well with the clinical activity and extent of disease in patients with El Bagre EPF.Abbreviations BMZ Basement membrane zone - BP Bullous pemphigoid - BP180 Bullous pemphigoid 180 kDa antigen - ConA Concanavalin A - CPF Cazanaves pemphigus foliaceus - DIF Direct immunofluorescence - ELISA Enzyme-linked immunosorbent assay - EPF Endemic pemphigus foliaceus - IB Immunoblotting - IIF Indirect immunofluorescence - IP Immunoprecipitation - mAb Monoclonal antibody - PBS Phosphate-buffered saline - PBS^– Phosphate-buffered saline lacking divalent cations - PF Pemphigus foliaceus - PV Pemphigus vulgaris - SLE Systemic lupus erythematosus This paper is part of the doctoral (PhD) thesis of Ana María Abréu Vélez, MD, while at the University of Antioquia.     

Neumann型增殖型天疱疮7例临床分析

目的 分析和总结Neumann型增殖型天疱疮的临床、病理、诊断及治疗特点.方法 回顾性分析2012年1月-2020年1月新疆自治区人民医院诊治的7例Neu-mann型增殖型天疱疮的临床资料.结果 7例患者腋窝、小腿内侧、腹股沟区、肛门等皱褶处出现肥厚性暗褐色斑块.皮损组织病理检查示:表皮显著增生,局灶性海绵水肿,表皮内...     

71例天疱疮的棘层松解位置分析

目的 探讨天疱疮的棘层松解位置,为天疱疮出现不同位置棘层松解的表现提供解释.方法 收集43例寻常型天疱疮和28例落叶型天疱疮患者的临床资料、组织病理、免疫病理、天疱疮抗体指标值进行分析.结果 寻常型天疱疮中有35例棘层松解的位置发生在基底层上方,8例发生在表皮中上部,落叶型天疱疮中有25例棘层松解的位置发生在颗粒层、棘层上方,3例发生在表皮中下部,落叶型天疱疮患者抗Dsg1抗体指标较寻常型天疱疮患者显著升高(P=0.047),寻常型天疱疮棘层松解的位置发生在表皮中上部的患者抗Dsg1、3抗体指标值与棘层松解发生在基底层上方的患者相比有差异,但无统计学意义.结论 寻常型天疱疮及落叶型天疱疮患者组织病理中,棘层松解的位置可发生于表皮中上部、表皮中下部.棘层松解的位置可能与抗Dsg1抗体和抗Dsg3抗体指标值等相关.     

Increased antibody levels to desmogleins 1 and 3 after administration of carbamazepine

Desmoglein (Dsg) 1 and Dsg3 are recognized as the autoantigens in pemphigus foliaceus and pemphigus vulgaris. Pemphigus-like syndromes have been reported to occur in individuals after exposure to a variety of drugs, but pemphigus caused by carbamazepine is not common. We found that anti-Dsg1 and anti-Dsg3 antibody titres were increased in three individuals administered carbamazepine. Antibody titres against Dsgs 1 and 3 were measured by enzyme-linked immunosorbent assay (ELISA). Of 42 serum samples (25 patients administered carbamazepine, eight patients administered valproic acid and nine healthy volunteers) tested by ELISA, three patients administered carbamazepine showed positive reactivity against both Dsg1 and Dsg3. The patient with the highest titre against Dsg1 and Dsg3 (the index values of anti-Dsg1 and anti-Dsg3 were 79.3 and 86.4, respectively) was a 23-year-old woman (Case 1). The other two patients with positive reactivity were a 5-year-old boy (Case 2) and a 65-year-old man (Case 3). In addition, indirect immunofluorescence study showed intercellular antibodies to the cell surface of the whole epidermis with a titre of 1 : 64 in Case 1 and 1 : 2 in Cases 2 and 3. However, no skin or mucosal involvement was found in any of these cases. There was no difference in the serum concentrations of carbamazepine between the three positive cases and the 22 negative cases of carbamazepine administration. From these facts, the lack of skin diseases may be explained by relatively low values of anti-Dsg 1 and 3 antibodies in Cases 2 and 3. However, it cannot be excluded that undefined exogenous and/or endogenous factors are involved in an outbreak of pemphigus. Furthermore, these findings might be helpful for preventing susceptible individuals from exposure to the suspect drugs.     

天疱疮特异性抗体亚型与疾病活动的相关性研究

目的 探讨天疱疮患者抗桥粒芯糖蛋白（Dsg）1和Dsg3抗体亚型与疾病活动的相关性。方法 收集47例天疱疮患者血清,ELISA检测其特异性抗Dsg1和Dsg3抗体及亚型,分析抗体滴度及亚型与疾病活动的相关性。结果 抗Dsg1和Dsg3抗体类别与天疱疮临床类型有关,17例皮肤黏膜同时受累的患者中有14例（82.4%）同时存在两种抗体;16例仅皮肤受累的患者中有15例（93.7%）存在抗Dsg1抗体,仅1例（6.3%）存在抗Dsg3抗体;6例仅黏膜受累的患者只存在抗Dsg3抗体,阳性率为100％。随着病情的加重,抗Dsg1和Dsg3抗体滴度有上升趋势,但该趋势与疾病的严重度并不完全平行。而抗体亚型则和疾病活动相关,活动期以特异性IgG4亚型为主,稳定期以IgG1亚型为主。抗Dsg1阳性者,活动期特异性IgG4和IgG1抗体吸光度（A）值分别为1.92 ± 1.21和0.60 ± 0.61,IgG4/IgG1 > 1;稳定期特异性IgG4和IgG1抗体A值分别为0.03 ± 0.02和0.22 ± 0.11,IgG4/IgG1 < 1;抗Dsg3阳性者,活动期特异性IgG4和IgG1抗体A值分别为2.35 ± 2.17和1.84 ± 1.16,IgG4/IgG1 > 1;稳定期特异性IgG4和IgG1抗体A值分别为0.15 ± 0.16和1.05 ± 0.77,IgG4/IgG1 < 1。结论 天疱疮特异性抗体亚型与疾病活动密切相关,用ELISA检测天疱疮患者血清中抗Dsg1和Dsg3抗体类型、特异性抗体亚型及滴度,可更好地辅助诊断疾病、监测疾病活动。     

Comparison of an indirect immunofluorescence assay and a modified sensitive immunoblot assay for the study of the autoantibody in pemphigus vulgaris

Some patients with pemphigus vulgaris (PV) have positive direct immunofluorescence (DIF) but are negative by indirect immunofluorescence (IIF). The purpose of this study was (1) to compare the sensitivity of an IIF assay with an immunoblot (IB) assay, (2) to compare the IIF and the IB assay in PV patients in whom the clinical picture and DIF were consistent, but the IIF was negative and (3) to compare the IIF and the IB assay in patients in clinical remission for 3 years or more. A comparison was made of the titers of PV autoantibody in the IIF assay using monkey esophagus as substrate and the modified sensitive IB assay using preabsorbed normal human skin lysate and COLO-16 lysate as a substrate in the three groups of patients. The sensitivity of the Western blot was enhanced by modifications in the extraction procedure of the lysate, by absorption of lysate with normal human serum and by the use of an enzygraphic web. In group 1, comprising 23 PV patients with active generalized disease, the titers of the autoantibody in the IB assay were 2–4-fold higher than in the IIF assay. This difference was highly significant (P=0.0001). In group 2, comprising 10 patients with limited or minimal PV who were positive on DIF and negative on IIF, all the patients were positive in the IB assay. In group 3, comprising 9 patients clinically free of disease and off all therapy for at least 3 years and negative in IIF assay, all the patients were positive in the IB assay. An additional two such patients who had low titers in the IIF assay had significantly higher titers in the IB assay. In the IB assay normal human skin and COLO-16 cell lines produced similar results even though PV sera bound to a 130 kDa protein on normal human skin lysate and a 105 kDa protein on COLO-16 lysate. The availability of this modified sensitive IB assay will have significant clinical benefit in the diagnosis of PV patients when IIF is negative, and in the study of autoantibody production.