An attempt to develop mouse model for anti-laminin γ1 pemphigoid.

We recently reported that the autoantibodies of anti-p200 pemphigoid sera react with laminin γ1 and renamed this entity as anti-laminin γ1 pemphigoid. However, it has not been clarified whether the anti-laminin γ1 autoantibodies, particularly those to the C-terminal integrin binding site, affect the dermoepidermal junction and cause subepidermal blisters. The aim of this study was to develop animal models for anti-laminin γ1 pemphigoid. We attempted to produce two mouse models for anti-laminin γ1 pemphigoid; (1) a passive transfer model: injection of rabbit IgG to shorter bacterial recombinant protein of the murine laminin γ1 C-terminal 107 amino acids, and (2) an active disease model: direct immunization to mice with this recombinant protein. Immunoblotting revealed that 70% of patient sera reacted with the shorter recombinant protein of human laminin γ1 C-terminus. In the passive transfer model, rabbit IgG to the murine laminin γ1 C-terminus was deposited, without C3 deposition, at the epidermal basement membrane zone. In contrast, in the active disease model, direct immunofluorescence of mouse skin sections showed no deposition of either murine IgG or C3. Blister formation was not seen in either model both phenotypically and histopathologically. In the two different mouse animal models for anti-laminin γ1 pemphigoid, although rabbit IgG to the recombinant laminin γ1 C-terminus bound to the epidermal basement membrane zone in passive transfer model, no obvious blister formation was seen. To reproduce skin lesions in mouse models for anti-laminin γ1 pemphigoid, further improvement should be needed.

Koga H ，Ishii N ，Dainichi T ，Tsuruta D ，Hamada T ，Ohata C ，Karashima T ，Furumura M ，Hashimoto T ... -  《-》

Pathogenicity of autoantibodies in anti-p200 pemphigoid.

Vafia K ，Groth S ，Beckmann T ，Hirose M ，Dworschak J ，Recke A ，Ludwig RJ ，Hashimoto T ，Zillikens D ，Schmidt E ... -  《PLoS One》

Anti-p200 pemphigoid.

Anti-p200 pemphigoid is a rare subepidermal blistering skin disease. Patients' autoantibodies label the dermal side of 1 mol/L NaCl-split human skin by indirect immunofluorescence microscopy and recognize a 200-kd protein by immunoblotting of human dermal extract. Clinically, anti-p200 pemphigoid is characterized by tense blisters and vesicles, erosions, and urticarial plaques, closely resembling bullous pemphigoid and the inflammatory variant of epidermolysis bullosa acquisita. Recently, 90% of anti-p200 pemphigoid sera were shown to recognize laminin γ1. The C-terminus of laminin γ1 was identified as an immunodominant region and in its recombinant form was used by immunoblotting and enzyme-linked immunosorbent assay for the serologic diagnosis of this disease. Subsequent ex vivo and in vivo studies were, however, unable to show pathogenic activity of antilaminin γ1 antibodies. Both patients' sera and sera depleted from antilaminin γ1 antibodies induced subepidermal splitting in an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation. Antilaminin γ1 antibodies appear to be useful biomarkers that will further facilitate the diagnosis of anti-p200 pemphigoid. The true identity of the pathogenetically relevant autoantigen of this disease, which may either be a yet unknown isoform of laminin γ1 or even another 200-kd protein of the dermoepidermal junction, still needs to be elucidated.

Goletz S ，Hashimoto T ，Zillikens D ，Schmidt E ... -  《-》

From anti-p200 pemphigoid to anti-laminin gamma1 pemphigoid.

Dainichi T ，Koga H ，Tsuji T ，Ishii N ，Ohyama B ，Ueda A ，Natsuaki Y ，Karashima T ，Nakama T ，Yasumoto S ，Zillikens D ，Hashimoto T ... -  《-》

IgA anti-p200 pemphigoid.

Wozniak K ，Hashimoto T ，Fukuda S ，Ohyama B ，Ishii N ，Koga H ，Dainichi T ，Kowalewski C ... -  《-》