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The following is a summary of “Anti-Laminin β4 IgG Drives Tissue Damage in Anti-p200 Pemphigoid and Shows Interactions with Laminin α3 and γ1/2 Chains,” published in the April 2025 issue of Journal of Investigative Dermatology by Pigors et al. 

Laminin β4 had recently been identified as a structural component of the dermal-epidermal junction and an autoantigen in anti-p200 pemphigoid.  

Researchers conducted a retrospective study to provide further evidence of the pathogenic effect of anti-laminin β4 IgG and identify potential binding partners of laminin β4.  

They demonstrated that laminin β4 immune complexes activated normal leukocytes and triggered dose-dependent ROS release. Cryosection analysis of normal skin revealed that anti-laminin β4 serum IgG caused dermal-epidermal separation in the presence of leukocytes, while anti-laminin γ1 IgG did not. Proximity ligation assay and indirect immunofluorescence staining showed that laminin β4 closely localized with laminin α3 and γ2 in primary keratinocytes. Coimmunoprecipitation of epidermal extracts confirmed the interaction between laminin β4 and the α3 and γ2 chains, with additional binding to laminin γ1. Laminin β4-α3/β4-γ1 protein complexes were detected via mass spectrometry.  

The results showed that laminin β4 immune complexes induced leukocyte activation and ROS release, resulting in dermal-epidermal separation when leukocytes were present. Laminin β4 was found to interact closely with laminin α3 and γ2 in primary keratinocytes, while also showing additional binding to laminin γ1.  

Investigators concluded that anti-laminin β4 IgG contributed to skin tissue damage, supporting its pathogenic role in anti-p200 pemphigoid, while evidence for its interaction with laminin α3 was strong, but its association with laminin γ1 and γ2 chains remained unclear. 

Source: jidonline.org/article/S0022-202X(24)02054-2/fulltext