Lamb Philina M, Patton Timothy, Deng Jau-Shyong
Department of Dermatology, University of California, Davis, Sacramento, California, USA.
Int J Dermatol. 2008 Feb;47(2):150-3. doi: 10.1111/j.1365-4632.2008.03361.x.
Prodromal bullous pemphigoid (PBP) and bullous pemphigoid (BP) demonstrate immunoglobulin G (IgG) and/or C3 deposition at the basement membrane zone (BMZ) on direct immunofluorescence. BP-180-specific IgG1, IgG4, and IgE antibodies have been detected in BP. However, the distribution of IgG subclasses is unknown in PBP.
We will describe the role of anti-BMZ IgG subclasses in PBP and we will correlate these findings to better understand the pathogenesis of PBP.
Skin biopsies and serum samples were obtained from 45 patients who had PBP. The skin tissue was processed for direct immunofluorescence studies. Sera were analyzed by indirect immunofluorescence for the presence of circulating anti-BMZ IgG antibodies (by standard IIF) and IgG subclasses antibodies (by sandwich double antibody immunofluorescence [SDAI]). Sera were also analyzed for antibodies against BP-180 and BP-230 antigens by enzyme-linked immunosorbent assay (ELISA).
Thirty-two patients (71%) had IgG and C3 staining at the BMZ, while 13 patients (29%) had isolated C3 staining at the BMZ on direct immunofluorescence. All patients demonstrated staining on the epidermal side of the salt-split skin. Of the seven skin specimens that were available for C5-9 SDAI testing, all were found to be positive along BMZ area. Standard IIF studies demonstrated the presence of circulating BMZ antibodies in 11 of the 30 patients (36.6%). When SDAI for IgG subclass differentiation was utilized, 17 of 30 (56.6%) patients were found to have circulating anti-BMZ antibodies. All of these 17 patients had IgG4 subclass antibodies. Thirteen patients did not have detectable IgG subclass anti-BMZ antibody on SDAI. Sixteen of 30 patients had detectable anti-BP-180 or anti-BP-230 antibodies, while 12 (40%) did not have detectable antibody against BP antigens on ELISA.
IgG4 is the initial and predominant anti-BMZ antibody subclass detected in PBP. Demonstration of linear C5-9 at the BMZ enhances the early diagnosis of PBP. Predominance of IgG4 and the initial presence of IgG4 on skin lesions as well as the presence of only IgG4 subclass anti-BMZ antibody suggest that IgG4 subclass antibody could be the initial immunologic event encountered in patients with PBP.
前驱大疱性类天疱疮（PBP）和大疱性类天疱疮（BP）在直接免疫荧光检查中显示免疫球蛋白G（IgG）和/或C3沉积于基底膜带（BMZ）。在BP中已检测到BP180特异性IgG1、IgG4和IgE抗体。然而，PBP中IgG亚类的分布尚不清楚。
我们将描述抗BMZ IgG亚类在PBP中的作用，并将这些发现相互关联以更好地理解PBP的发病机制。
从45例PBP患者中获取皮肤活检组织和血清样本。对皮肤组织进行直接免疫荧光研究。通过间接免疫荧光分析血清中循环抗BMZ IgG抗体（通过标准间接免疫荧光法[IIF]）和IgG亚类抗体（通过夹心双抗体免疫荧光法[SDAI]）的存在情况。还通过酶联免疫吸附测定（ELISA）分析血清中抗BP180和BP230抗原的抗体。
32例患者（71%）在BMZ处有IgG和C3染色，而13例患者（29%）在直接免疫荧光检查中BMZ处仅有C3染色。所有患者在盐裂皮肤的表皮侧均显示染色。在可用于C5-9 SDAI检测的7份皮肤标本中，所有标本在BMZ区域均呈阳性。标准IIF研究显示30例患者中有11例（36.6%）存在循环BMZ抗体。当采用SDAI进行IgG亚类区分时，30例患者中有17例（56.6%）被发现存在循环抗BMZ抗体。这17例患者均有IgG4亚类抗体。13例患者在SDAI检测中未检测到IgG亚类抗BMZ抗体。30例患者中有16例检测到抗BP180或抗BP230抗体，而12例（40%）在ELISA检测中未检测到抗BP抗原的抗体。
IgG4是在PBP中检测到的初始且主要的抗BMZ抗体亚类。BMZ处线性C5-9的显示可提高PBP的早期诊断。IgG4的优势以及皮肤病变上IgG4的初始存在以及仅存在IgG4亚类抗BMZ抗体表明IgG4亚类抗体可能是PBP患者中最初遇到的免疫事件。
