Human epiligrin, also known as laminin-332, laminin-5, nicein, kalinin, or BM-600 is a basement membrane glycoprotein complex essential for epithelial adhesion, wound healing, and integrity of skin and mucosal tissues. Because of its multiple chain structure and involvement in autoimmune disease and inherited blistering disorders, epiligrin is a topic of increasing interest in immunodermatology, molecular pathology, and therapeutic research.

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1. Epiligrin (laminin-332) is a heterotrimer composed of three chains : α3, β3, and γ2. Learn more on Pubmed.
2. Genes encoding these chains include LAMA3 (for α3), LAMB3, LAMC2. Mutations or dysregulation can cause defects in structure or function.
3. This molecule is secreted by keratinocytes and integrated into the basement membrane zone (BMZ) between the epidermis and dermis (skin) and also in mucosal tissues.
4. The protein domain architecture includes a long “coiled-coil” region for trimerization, and globular domains (“G domains”) especially in the α3 chain that are involved in interactions with cell surface receptors (e.g. integrins).

1. Cell adhesion : Laminin-332 mediates adhesion of basal epithelial cells via integrin receptors notably α6β4 and α3β1 integrins. This is crucial in hemidesmosomes and cell-basement membrane anchorage.
2. Wound healing & migration : It supports keratinocyte migration, spreading, and re-epithelialization following injury. The processed laminin-332 fragments influence cell behavior including migration and adhesion.
3. Barrier integrity : In skin and mucosa, epiligrin contributes to the structure of anchoring filaments/fibers that stabilize the epidermal-dermal or epithelial-connective tissue boundary. Disruption leads to fragility.

NCBI

1. Mutations in LAMA3, LAMB3, LAMC2 can cause junctional epidermolysis bullosa (JEB), a set of inherited skin blistering disorders marked by defective adhesion. Particularly severe forms are associated with mutations in the α3 chain (LAMA3).
2. Common variants affecting expression, glycosylation, secretion, or chain assembly have been investigated in molecular diagnostic settings.

Complexity of Transcriptional and Translational Interference of Laminin-332 Subunits in Junctional Epidermolysis Bullosa with LAMB3 Mutations :

1. Disease definition : Anti-epiligrin cicatricial pemphigoid (AECP) or anti-laminin-332 mucous membrane pemphigoid is an autoimmune blistering disorder targeting laminin-332 (epiligrin) in BMZ. It affects mucosal surfaces (oral, ocular, laryngeal etc.), often with scarring. NCBI
2. Autoantibody specificity : Though many patients have IgG autoantibodies against the α3 chain or its G-domains, some also have antibodies against β3 or γ2 subunits. NCBI
3. Epitope mapping : Sera from AECP patients often recognize particular domains (especially the G domains) of the α3 subunit. Immunoblotting with recombinant fragments confirms that.
4. Clinical features & risks : Disease presents with mucosal blistering, scarring; ocular involvement can lead to blindness; laryngeal involvement can threaten airway. Notably, some studies show association with malignancy in patients with anti-laminin-332 autoantibodies.

1. Indirect immunofluorescence (IIF) on substrate (e.g. salt-split skin) : to detect circulating autoantibodies binding to BMZ. AECP sera often bind the epidermal side of split skin; confirmation via binding to laminin-332.

1. Immunoblotting / immunoprecipitation : Using cultured keratinocyte extracts, recombinant fragments (especially of the α3 chain) to determine which subunit(s) are targeted.
2. Molecular genetics : For inherited disorders involving laminin-332 (e.g. JEB), sequencing of LAMA3, LAMB3, LAMC2 genes, analysis of splice variants/mutations.
3. Histology / electron microscopy : Localization of basement membrane splitting, blister formation site, ultrastructure of BMZ anchoring complex.

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1. Disease variant identification matters : Subsets of mucous membrane pemphigoid defined by anti-laminin-332 autoantibodies often have different prognosis, severity, and risk of associated malignancy. Thus accurate diagnosis of epiligrin autoimmunity could guide surveillance. NCBI
2. Treatment considerations : As with other autoimmune blistering diseases, immunosuppressive therapy is often used; severity and mucosal involvement influence choice of systemic therapy. Monitoring autoantibody titers and antigen specificity may influence management.
3. Cancer association : Some retrospective cohort data suggest that patients with anti-laminin-332 autoantibodies have higher incidence of solid tumors compared to general population. Whether epiligrin autoimmunity is paraneoplastic in some cases is subject of ongoing research. ScienceDirecte

1. Epiligrin (laminin-332) is a critical basement membrane protein composed of three chains, essential for adhesion, wound healing, and basement membrane structure.
2. Mutations in its genes cause inherited blistering (JEB), while autoantibodies against it cause cicatricial pemphigoid / mucous membrane pemphigoid variants.
3. Accurate diagnosis via immunofluorescence, immunoblotting, molecular genetics is required. Antibody subunit specificity (α3, β3, γ2) and epitope mapping provide prognostic and therapeutic relevance.
4. Emerging evidence suggests that disease subsets with anti-laminin-332 autoantibodies may carry increased malignancy risk.