| First Author | Florea F | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 2 | Pages | 494-506 |
| PubMed ID | 24300951 | Mgi Jnum | J:208064 |
| Mgi Id | MGI:5560853 | Doi | 10.1016/j.ajpath.2013.10.019 |
| Citation | Florea F, et al. (2014) Ex vivo pathogenicity of anti-laminin gamma1 autoantibodies. Am J Pathol 184(2):494-506 |
| abstractText | Autoimmunity against laminins has been described in several autoimmune diseases (including mucous membrane pemphigoid, anti-laminin gamma1 pemphigoid, and connective tissue diseases), in pregnancy loss, and in infections such as Chagas disease. Except for anti-laminin-332 mucous membrane pemphigoid, adequate evidence has been lacking for the tissue injury potential of laminin-specific antibodies and the pathogenic epitopes. We evaluated the pathogenic potential of antibodies targeting laminin gamma1, a major constituent of basement membranes and the main antigen in anti-laminin gamma1 pemphigoid. Rabbit antibodies were generated against fragments of the N-terminus and C-terminus of murine laminin gamma1, and their ability to disrupt ligand interactions and/or to activate complement and granulocytes was assessed using previously established ex vivo assays. Our findings document a pathogenic potential of antibodies targeting the laminin gamma1 N-terminus. These antibodies interfere with the binding of nidogen to laminin and can activate granulocytes and the complement cascade. We detected antibodies with different degrees of reactivity with laminin gamma1 N-terminus in patients with anti-laminin gamma1 pemphigoid, cutaneous lupus erythematosus, and scleroderma. Our results provide mechanistic insights into the tissue damage associated with laminin autoimmunity and could facilitate development of appropriate diagnostic tools and therapeutic strategies. |
