Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid

Background: Anti -p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin g 1 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 g 1 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 /3 4 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 /3 4 is the diagnostically relevant antigen of anti -p200 pemphigoid. Conclusion: The identification of laminin /3 4 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. ( J Am Acad Dermatol 2024;90:790-7.)