Ex Vivo Pathogenicity of Anti-Laminin gamma 1 Autoantibodies

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

Оптический датчик температуры на основе нанокристаллической пленки SiC

На основе нанокристаллических пленок кубического политипа карбида кремния, полученных прямым ионным осаждением на подложке из лейкосапфира, разработан интерференционный датчик температуры

Structural elucidation of full-length nidogen and the laminin-nidogen complex in solution

Nidogen-1 is a key basement membrane protein that is required for many biological activities. It is one of the central elements in organizing basal laminae including those in the skin, muscle, and the nervous system. The self-assembling extracellular matrix that also incorporates fibulins, fibronectin and integrins is clamped together by networks formed between nidogen, perlecan, laminin and collagen IV. To date, the full-length version of nidogen-1 has not been studied in detail in terms of its solution conformation and shape because of its susceptibility to proteolysis. In the current study, we have expressed and purified full-length nidogen-1 and have investigated its solution behavior using size-exclusion chromatography (SEC), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). The ab initio shape reconstruction of the complex between nidogen-1 and the laminin γ-1 short arm confirms that the interaction is mediated solely by the C-terminal domains: the rest of the domains of both proteins do not participate in complex formation