BACKGROUND: Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease where autoantibodies target various components of the dermal-epidermal junction, including the bullous pemphigoid antigen 180 (BP180). OBJECTIVE: We determined the exact specificity of circulating IgG and IgA autoantibodies to BP180 in a large number of CP patients. METHODS: Twenty-six consecutive CP sera were analysed by Western blotting using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule. RESULTS: Circulating autoantibodies were detected in all CP sera. Seven sera reacting with laminin-5 were excluded from further analyses; the remaining 19 sera recognized BP180, including six sera (32%) that showed only IgA reactivity to this protein. With the combined use of the soluble BP180 ectodomain (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targeted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the BP180-reative sera revealed reactivity with the intracellular domain of this protein. CONCLUSIONS: Our findings demonstrate that autoantibodies in CP target epitopes on both extra- and intracellular domains of BP180 and highlight the importance of testing for both IgG and IgA reactivity in these patients' sera.
BACKGROUND: Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease where autoantibodies target various components of the dermal-epidermal junction, including the bullous pemphigoid antigen 180 (BP180). OBJECTIVE: We determined the exact specificity of circulating IgG and IgA autoantibodies to BP180 in a large number of CP patients. METHODS: Twenty-six consecutive CP sera were analysed by Western blotting using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule. RESULTS: Circulating autoantibodies were detected in all CP sera. Seven sera reacting with laminin-5 were excluded from further analyses; the remaining 19 sera recognized BP180, including six sera (32%) that showed only IgA reactivity to this protein. With the combined use of the soluble BP180 ectodomain (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targeted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the BP180-reative sera revealed reactivity with the intracellular domain of this protein. CONCLUSIONS: Our findings demonstrate that autoantibodies in CP target epitopes on both extra- and intracellular domains of BP180 and highlight the importance of testing for both IgG and IgA reactivity in these patients' sera.
Authors: Valerie P J Saw; Enno Schmidt; Ifeoma Offiah; Grazyna Galatowicz; Detlef Zillikens; John K G Dart; Virginia L Calder; Julie T Daniels Journal: Am J Pathol Date: 2010-12-23 Impact factor: 4.307
Authors: Nina van Beek; Kristin Rentzsch; Christian Probst; Lars Komorowski; Michael Kasperkiewicz; Kai Fechner; Inga M Bloecker; Detlef Zillikens; Winfried Stöcker; Enno Schmidt Journal: Orphanet J Rare Dis Date: 2012-08-09 Impact factor: 4.123