Universität zu Köln

Florea, Florina, Bernards, Claudia, Caproni, Marzia, Kleindienst, Jessika, Hashimoto, Takashi ORCID: 0000-0002-0144-3255, Koch, Manuel ORCID: 0000-0002-2962-7814 and Sitaru, Cassian ORCID: 0000-0002-0370-1270 (2014). Ex Vivo Pathogenicity of Anti-Laminin gamma 1 Autoantibodies. Am. J. Pathol., 184 (2). S. 494 - 507. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

Autoimmunity against laminins has been described in several autoimmune diseases (including mucous membrane pemphigoid, anti laminin gamma 1 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 gamma 1, a major constituent of basement membranes and the main antigen in anti Laminin gamma 1 pemphigoid. Rabbit antibodies were generated against fragments of the N-terminus and C-terminus of murine laminin gamma 1, 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 gamma 1 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 gamma 1 N-terminus in patients with anti Laminin gamma 1 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Florea, Florina UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernards, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Caproni, Marzia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleindienst, Jessika UNSPECIFIED UNSPECIFIED UNSPECIFIED Hashimoto, Takashi UNSPECIFIED orcid.org/0000-0002-0144-3255 UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Sitaru, Cassian UNSPECIFIED orcid.org/0000-0002-0370-1270 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-447275
DOI:	10.1016/j.ajpath.2013.10.019
Journal or Publication Title:	Am. J. Pathol.
Volume:	184
Number:	2
Page Range:	S. 494 - 507
Date:	2014
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CUTANEOUS LUPUS-ERYTHEMATOSUS; BASEMENT-MEMBRANES; NIDOGEN-BINDING; PASSIVE TRANSFER; MOUSE MODEL; ANTIBODIES; COLLAGEN; MICE; RAT; MECHANISMS Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44727