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Serological Studies in Bullous Pemphigoid: A Literature Review of Antibody Titers at Presentation and in Clinical Remission

doi: 10.2340/00015555-0819


Bullous pemphigoid is associated with antibodies to a 230 kDa and a 180 kDa protein. In a literature review we investigated the role of auto-antibodies as detected by different serological assays. Nine reports containing data on 143 patients were analyzed. Pre-treatment data showed that indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and immunoblotting offer an 82.2% or greater probability of being positive. At the end of the study period, all patients had clinically improved, whether or not they were on therapy. Auto-antibodies were present in 29% of patients evaluated by monkey esophagus immunofluorescence and 75% of those evaluated by human skin immunofluorescence. Positive titers were also reported in 67.6% of patients evaluated by ELISA. In 100% of patients in whom immunoblotting was performed the titers became negative. In 3 patients (5.3%) using human skin immunofluorescence and in one patient (1.4%) using ELISA the titers were increased at the end of the study period. The correlation between anti-basement membrane zone antibodies and the clinical course of bullous pemphigoid requires further and long-term studies.


Stefania Leuci, Hakan M. Gürcan, A. Razzaque Ahmed


  • Korman NJ. Bullous pemphigoid. The latest in diagnosis, prognosis, and therapy. Arch Dermatol 1998; 134: 1137–1141.
  • Nanda A, Al-Saeid K, Al-Sabah H, Dvorak R, Alsaleh QA. Clinicoepidemiological features and course of 43 cases of bullous pemphigoid in Kuwait. Clin Exp Dermatol 2006; 31: 339–342.
  • Gudi VS, White MI, Cruickshank N, Herriot R, Edwards SL, Nimmo F. Cruickshank N, et al. Annual incidence and mortality of bullous pemphigoid in the Grampian Region of North-east Scotland. Br J Dermatol 2005; 153: 424–427.
  • Lever WF. Pemphigus and pemphigoid. A review of the advances made since 1964. J Am Acad Dermatol 1979; 1: 2–31.
  • Stanley JR, Hawley-Nelson P, Yuspa SH, Shevach EM, Katz SI. Characterization of bullous pemphigoid antigen: a unique basement membrane protein of stratified squamous epithelia. Cell 1981; 24: 897–903.
  • Labib RS, Anhalt GJ, Patel HP, Mutasim DF, Diaz LA. Molecular heterogeneity of the bullous pemphigoid antigens as detected by immunoblotting. J Immunol 1986; 136: 1231–1235.
  • Borradori L, Chavanas S, Schaapveld RQ, Gagnoux-Palacios L, Calafat J, Meneguzzi G, et al. Role of the bullous pemphigoid antigen 180 (BP180) in the assembly of hemidesmosomes and cell adhesion – reexpression of BP180 in generalized atrophic benign epidermolysis bullosa keratinocytes. Exp Cell Res 1998; 239: 463–476.
  • Liu Z, Diaz LA, Troy JL, Taylor AF, Emery DJ, Fairley JA, et al. A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen BP180. J Clin Invest 1993; 92: 2480–2488.
  • Liu Z, Giudice GJ, Swartz SJ, Fairley JA, Till GO, Troy JL, et al. The role of complement in experimental bullous pemphigoid. J Clin Invest 1995; 95: 1539–1544.
  • Hall RP 3rd, Murray JC, McCord MM, Rico MJ, Streilein RD. Rabbits immunized with a peptide encoded for by the 230-kD bullous pemphigoid antigen cDNA develop an enhanced inflammatory response to UVB irradiation: a potential animal model for bullous pemphigoid. J Invest Dermatol 1993; 101: 9–14.
  • Ishiura N, Fujimoto M, Watanabe R, Nakashima H, Kuwano Y, Yazawa N, et al. Serum levels of IgE anti-BP180 and anti-BP230 autoantibodies in patients with bullous pemphigoid. J Dermatol Sci 2008; 49: 153–161.
  • Schmidt E, Obe K, Bröcker EB, Zillikens D. Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Arch Dermatol 2000; 136: 174–178.
  • Cheng SW, Kobayashi M, Kinoshita-Kuroda K, Tanikawa A, Amagai M, Nishikawa T. Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3. Br J Dermatol 2002; 147: 261–265.
  • Sams WM Jr, Jordon RE. Correlation of pemphigoid and pemphigus antibody titres with activity of disease. Br J Dermatol 1971; 84: 7–13.
  • Remy W, Bockendahl H, Stüttgen G. Immunofluorescent follow-up studies in patients with bullous dermatoses. Acta Derm Venereol 1975; 55: 117–120.
  • Ahmed AR, Maize JC, Provost TT. Bullous pemphigoid. Clinical and immunologic follow-up after successful therapy. Arch Dermatol 1977; 113: 1043–1046.
  • Hadi SM, Barnetson RS, Gawkrodger DJ, Saxena U, Bird P, Merrett TG. Clinical, histological and immunological studies in 50 patients with bullous pemphigoid. Dermatologica 1988; 176: 6–17.
  • Venning VA, Wojnarowska F. Lack of predictive factors for the clinical course of bullous pemphigoid. J Am Acad Dermatol 1992; 26: 585–589.
  • Amo Y, Ohkawa T, Tatsuta M, Hamada Y, Fujimura T, Katsuoka K, et al. Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid. J Dermatol Sci 2001; 26: 14–18.
  • Kobayashi M, Amagai M, Kuroda-Kinoshita K, Hashimoto T, Shirakata Y, Hashimoto K, et al. BP180 ELISA using bacterial recombinant NC16a protein as a diagnostic and monitoring tool for bullous pemphigoid. J Dermatol Sci 2002; 30: 224–232.
  • Sami N, Ali S, Bhol KC, Ahmed AR. Influence of intravenous immunoglobulin therapy on autoantibody titres to BP Ag1 and BP Ag2 in patients with bullous pemphigoid. J Eur Acad Dermatol Venereol 2003; 17: 641–645.
  • Izumi T, Ichiki Y, Esaki C, Kitajima Y. Monitoring of ELISA for anti-BP180 antibodies: clinical and therapeutic analysis of steroid-treated patients with bullous pemphigoid. J Dermatol 2004; 31: 383–391.
  • Tsuji-Abe Y, Akiyama M, Yamanaka Y, Kikuchi T, Sato-Matsumura KC, Shimizu H. Correlation of clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA kit in bullous pemphigoid. J Dermatol Sci 2005; 37: 145–149.
  • Feng S, Wu Q, Jin P, Lin L, Zhou W, Sang H, Shao C. Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Int J Dermatol 2008; 47: 225–228.
  • Giudice GJ, Wilske KC, Anhalt GJ, Fairley JA, Taylor AF, Emery DJ, et al. Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid and herpes gestationis. J Invest Dermatol 1994; 102: 878–881.
  • Zillikens D, Mascaro JM, Rose PA, Liu Z, Ewing SM, Caux F, et al. A highly sensitive enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid. J Invest Dermatol 1997; 109: 679–683.
  • Sakuma-Oyama Y, Powell AM, Oyama N, Albert S, Bhogal BS, Black MM. Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid. Br J Dermatol 2004; 151: 126–131.
  • Powell AM, Sakuma-Oyama Y, Oyama N, Albert S, Bhogal B, Kaneko F, et al. Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy. Arch Dermatol 2005; 141: 705–710.
  • Barnadas MA, Rubiales MV, González MJ, Puig L, García P, Baselga E, et al. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence testing in a bullous pemphigoid and pemphigoid gestationis. Int J Dermatol 2008; 47: 1245–1249.
  • Di Zenzo G, Thoma-Uszynski S, Fontao L, Calabresi V, Hofmann SC, Hellmark T, et al. Multicenter prospective study of the humoral autoimmune response in bullous pemphigoid. Clin Immunol 2008; 128: 415–426.
  • Giudice GJ, Wilske KC, Anhalt GJ, Fairley JA, Taylor AF, Emery DJ, et al. Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid and herpes gestationis. J Invest Dermatol 1994; 102: 878–881.
  • Zillikens D, Rose PA, Balding SD, Liu Z, Olague-Marchan M, Diaz LA, et al. Tight clustering of extracellular BP180 epitopes recognized by bullous pemphigoid autoantibodies. J Invest Dermatol 1997; 109: 573–579.
  • Di Zenzo G, Grosso F, Terracina M, Mariotti F, De Pità O, Owaribe K, et al. Characterization of the anti-BP180 autoantibody reactivity profile and epitope mapping in bullous pemphigoid patients. J Invest Dermatol 2004; 122: 103–110.
  • Perriard J, Jaunin F, Favre B, Büdinger L, Hertl M, Saurat JH, et al. IgG autoantibodies from bullous pemphigoid (BP) patients bind antigenic sites on both the extracellular and the intracellular domains of the BP antigen 180. J Invest Dermatol 1999; 112: 141–147.
  • Suzuki M, Harada S, Yaoita H. Purification of bullous pemphigoid IgG subclasses and their capability for complement fixation. Acta Derm Venereol 1992; 72: 245–249.
  • Sitaru C, Mihai S, Zillikens D. The relevance of the IgG subclass of autoantibodies for blister induction in autoimmune bullous skin diseases. Arch Dermatol Res 2007; 299: 1–8.
  • Mihai S, Chiriac MT, Herrero-González JE, Goodall M, Jefferis R, Savage CO, et al. IgG4 autoantibodies induce dermal-epidermal separation. J Cell Mol Med 2007; 11: 1117–1128.
  • Slifka MK, Ahmed R. Long-lived plasma cells: a mechanism for maintaining persistent antibody production. Curr Opin Immunol 1998; 10: 252–258.
  • Mamani-Matsuda M, Cosma A, Weller S, Faili A, Staib C, Garçon L, et al. The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells. Blood 2008; 111: 4653–4659.
  • Hoyer BF, Mumtaz IM, Yoshida T, Hiepe F, Radbruch A. How to cope with pathogenic long-lived plasma cells in autoimmune diseases. Ann Rheum Dis 2008; 67 Suppl 3: iii87–89.
  • Manz RA, Moser K, Burmester GR, Radbruch A, Hiepe F. Immunological memory stabilizing autoreactivity. Curr Top Microbiol Immunol 2006; 305: 241–257.
  • Hoyer BF, Manz RA, Radbruch A, Hiepe F. Long-lived plasma cells and their contribution to autoimmunity. Ann N Y Acad Sci 2005; 1050: 124–133.
  • Yoshida M, Hamada T, Amagai M, Hashimoto K, Uehara R, Yamaguchi K, et al. Enzyme-linked immunosorbent assay using bacterial recombinant proteins of human BP230 as a diagnostic tool for bullous pemphigoid. J Dermatol Sci 2006; 41: 21–30.
  • Döpp R, Schmidt E, Chimanovitch I, Leverkus M, Bröcker EB, Zillikens D. IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in Bullous pemphigoid: serum levels of these immunoglobulins reflect disease activity. J Am Acad Dermatol 2000; 42: 577–583.
  • Sitaru C, Dähnrich C, Probst C, Komorowski L, Blöcker I, Schmidt E, Schlumberger W, et al. Enzyme-linked immunosorbent assay using multimers of the 16th non-collagenous domain of the BP180 antigen for sensitive and specific detection of pemphigoid autoantibodies. Exp Dermatol 2007; 16: 770–777.
  • Nakama T, Ishii N, Ono F, Hamada T, Yasumoto S, Hashimoto T. Efficacy of interferon-gamma in patients with refractory bullous pemphigoid. J Dermatol 2007; 34: 737–745.
  • Kyndt X, Reumaux D, Bridoux F, Tribout B, Bataille P, Hachulla E, et al. Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis. Am J Med 1999; 106: 527–533.
  • Shibayama K, Ohyama Y, Yokota, Y Ohtsu S, Takubo N, Matsuura N. Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins in children with Graves’ disease. Endocr J 2005; 52: 505–510.
  • Schwarz M, Spector L, Gortler M, Weisshaus O, Glass-Marmor L, Karni A, et al. Serum anti-Glc(alpha1,4)Glc(alpha) antibodies as a biomarker for relapsing-remitting multiple sclerosis. J Neurol Sci 2006; 244: 59–68.
  • Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, Bodman-Smith M, et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 2003; 48: 2146–2154.
  • Cambridge G, Leandro MJ, Teodorescu M, Manson J, Rahman A, Isenberg DA, et al. B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum 2006; 54: 3612–3622.
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    Volume 90, Issue 2

    DOI: 10.2340/00015555-0819

    Pages: 115-121

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