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  • Title: The predominance of IgG4 in prodromal bullous pemphigoid.
    Author: Lamb PM, Patton T, Deng JS.
    Journal: Int J Dermatol; 2008 Feb; 47(2):150-3. PubMed ID: 18211485.
    Abstract:
    BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
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