Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid
Stephanie Goletz, Manuela Pigors, Tina Rastegar Lari, Christoph M. Hammers, Yao Wang, Shirin Emtenani, Monique Aumailley, Maike M. Holtsche, Felix Stang, Imke Weyers, Inke R. König, Cristina Has, Christiane Radzimski, Lars Komorowski, Detlef Zillikens, Enno Schmidt
Abstract
BACKGROUND: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies. OBJECTIVE: To identify a target antigen with higher clinical and diagnostic relevance. METHODS: Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed. RESULTS: Laminin β4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes. LIMITATIONS: A higher number of sera needs to be tested to verify that laminin β4 is the diagnostically relevant antigen of anti-p200 pemphigoid. CONCLUSION: The identification of laminin β4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.