Characterization of the antibody response in oesophageal cicatricial pemphigoid

Abstract

Cicatricial pemphigoid (CP) is a subepidermal, autoimmune bullous dermatosis. It is classified as a clinical subset of bullous pemphigoid (BP). However, it differs from BP in some significant ways: (i) in CP mucosal involvement with clinical scarring is prominent; (ii) there is a prominent IgA class antibody response alone or in addition to the IgG class antibody response; and (iii) there is a heterogeneous antibody response in CP, whereas in BP the majority of the antibodies are directed against a 180-kDa hemidesmosomal protein, bullous pemphigoid antigen 2 (BPAg2). Oesophageal involvement in CP is a rare, but often devastating manifestation. In this study we examined the humoral autoimmune response in oesophageal CP, in an attempt to characterize the autoantibody reactivity profile. We used direct and indirect immunofluorescence and Western immunoblotting using normal human skin and oesophagus substrates. We studied patient sera over time in order to search for evidence of epitope spreading in these patients. All patients had positive direct immunofluorescence of perilesional oesophageal epithelium. All patients had positive circulating antibasement membrane zone autoantibody titres. There was a significant IgA class in addition to an IgG class autoantibody response. IgA and IgG antibodies demonstrated significant reactivity with BPAg2 and the 97 kDa linear IgA disease antigen on Western immunoblot suggesting intraprotein epitope spreading. There was no evidence of interprotein epitope spreading over time. Our findings suggest that there is a heterogeneous antibody response in oesophageal CP with the predominant antigen being BPAg2.

Oesophageal involvement in 26 consecutive patients with mucous membrane pemphigoid

“…The oesophageal biopsies of our patients did not clearly show any typical subepithelial split or positive DIF. Published data are consistent with a low rate of DIF positivity, except for one study, and the only published case report on isolated oesophageal EBA with positive IEM…”

“…In the largest series with barium swallow for seven patients with classical MMP (previously called benign MM pemphigoid), no outcome information was given . Other series provided only immunological, or clinical, radiological and endoscopic findings, without any follow‐up information . Three studies comparable with ours reported clinical and radiological observations, with follow‐up in four, three and four patients, respectively …”

“…Herein, we have described in detail the symptomatology, endoscopic lesions, extraoesophageal involvement, immunology, treatments and follow‐up of 26 consecutive patients with MMP with symptomatic oesophageal involvement. Unlike MMP buccal, ocular and NT involvements, MMP oesophageal involvement has rarely been described in detail . In the largest series with barium swallow for seven patients with classical MMP (previously called benign MM pemphigoid), no outcome information was given .…”

“…It can be severe and associated with strictures, leading to malnutrition . To the best of our knowledge, no prospective studies (only case reports and seven small series of oesophageal involvement) have been published …”

Number III Mucous membrane pemphigoid

“…Some patients may have lesions of other stratified squamous epithelia such as of the larynx (Miziara et al , 2002; Whiteside et al , 2003), subglottis (Cole et al , 2000), oesophagus (Egan et al , 1999a; Sallout et al , 2000; Park et al , 2002), or nasal (Miziara et al , 2002), vulva (Ikegaya et al , 1999), penis (Fueston et al , 2002) or anus (Mutasim et al , 1993; Lilly et al , 1995), where scarring may cause serious complications. In rare cases, CP is disseminated (Provost et al , 1979; Kurzhals et al , 1995; Poon and McGrath, 1999).…”