Abstract
Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum (r = −0.077, p > 0.05) or in blister fluid (r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid (r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of the disease, but not in the early stages of medication.
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References
Brick KE, Weaver CH, Lohse CM et al (2014) Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009. J Am Acad Dermatol 71(1):92–99
Charneux J, Lorin J, Vitry F, Antonicelli F et al (2011) Usefulness of BP230 and BP180-NC16a enzyme-linked immunosorbent assays in the initial diagnosis of bullous pemphigoid: a retrospective study of 138 patients. Arch Dermatol 147:286–291
Daneshpazhooh M, Shahdi M, Aghaeepoor M et al (2004) A comparative study of antibody titers of blister fluid and serum in patients with subepidermal immunobullous diseases. Int J Dermatol 43:348–351
Fairley JA, Bream M, Fullenkamp C et al (2013) Missing the target: characterization of bullous pemphigoid patients who are negative using the BP180 enzyme-linked immunosorbant assay. J Am Acad Dermatol 68(3):395–403
Fairley JA, Burnett CT, Fu CL et al (2007) A pathogenic role for IgE in autoimmunity: bullous pemphigoid IgE reproduces the early phase of lesion development in human skin grafted to nu/nu mice. J Invest Dermatol 127:2605–2611
Fania L, Caldarola G, Muller R et al (2012) IgE recognition of bullous pemphigoid (BP)180 and BP230 in BP patients and elderly individuals with pruritic dermatoses. Clin Immunol 143:236–245
Giudice GJ, Emery DJ, Diaz LA (1992) Cloning and primary structural analysis of the bullous pemphigoid autoantigen BP180. J Invest Dermatol 99:243–250
Giudice GJ, Emery DJ, Zelickson BD et al (1993) Bullous pemphigoid and herpes gestationis autoantibodies recognize a common non-collagenous site on the BP180 ectodomain. J Immunol 151:5742–5750
Iwata H, Kamio N, Aoyama Y, Yamamoto Y et al (2009) IgG from patients with bullous pemphigoid depletes cultured keratinocytes of the 180-kDa bullous pemphigoid antigen (type XVII collagen) and weakens cell attachment. J Invest Dermatol 129:919–926
Iwata Y, Komura K, Kodera M et al (2008) Correlation of IgE autoantibody to BP180 with a severe form of bullous pemphigoid. Arch Dermatol 144:41–48
Messingham KA, Noe MH, Chapman MA et al (2009) A novel ELISA reveals high frequencies of BP180-specific IgE production in bullous pemphigoid. J Immunol Methods 346:18–25
Messingham KA, Onoh A, Vanderah EM et al (2012) Functional characterization of an IgE-class monoclonal antibody specific for the bullous pemphigoid autoantigen, BP180. Hybridoma (Larchmt) 31(2):111–117
Zillikens D, Rose PA, Balding SD et al (1997) Tight clustering of extracellular BP180 epitopes recognized by bullous pemphigoid autoantibodies. J Invest Dermatol 109:573–579
Zone JJ, Taylor T, Hull C et al (2007) IgE basement membrane zone antibodies induce eosinophil infiltration and histological blisters in engrafted human skin on SCID mice. J Invest Dermatol 127:1167–1174
Acknowledgments
The authors would like to thank Prof. Xu Qun for her help in statistical analysis and Prof. Liu Zhi for his help in the manuscript. This research effort was supported by grants from the National Natural Science Foundation of China (81071301, 81371731) and the Beijing Natural Science Foundation (7132203).
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Bing, L., Xiping, Z., Li, L. et al. Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid. Arch Dermatol Res 307, 849–854 (2015). https://doi.org/10.1007/s00403-015-1598-3
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DOI: https://doi.org/10.1007/s00403-015-1598-3