ABSTRACT
BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a severe autoimmune skin disease characterized by tissue-bound and circulating autoantibodies to type VII collagen, the major component of anchoring fibrils. When passively transferred into mice, rabbit IgG against type VII collagen induces Fc-dependent activation of complement, the recruitment of leucocytes into the skin, and subepidermal blistering. In addition to these inflammatory mechanisms, clinical and experimental evidence suggests that antibodies against type VII collagen might induce blisters by disrupting the ligand function of type VII collagen by an Fc-independent mechanism. OBJECTIVES: To study noninflammatory mechanisms of blister formation in experimental EBA. METHODS: We generated chicken IgY antibodies directed to recombinant type VII collagen and examined their pathogenic activity using ex vivo and animal models. RESULTS: Mice injected with these chicken IgY antibodies showed binding of the antibodies to the dermal-epidermal junction of skin sections. However, IgY antibodies did not fix complement C3 in enzyme-linked immunosorbent assay and immunofluorescence complement-binding assays. In addition, IgY antibodies did not induce dermal-epidermal separation ex vivo. Following their passive transfer into Balb/c mice, chicken IgY antibodies against type VII collagen bound at the dermal-epidermal junction, but, in contrast to rabbit IgG, did not fix complement C3, recruit granulocytes, or induce skin blisters. CONCLUSIONS: These findings demonstrate that binding of avian IgY to type VII collagen is not pathogenic in vivo and strongly suggest that in experimental EBA, antibodies to type VII collagen induce blisters not by direct disruption of the ligand function of type VII collagen, but rather by an Fc-dependent engagement of humoral and cellular inflammatory factors.
Subject(s)
Collagen Type VII/metabolism , Complement C3/immunology , Epidermolysis Bullosa Acquisita/immunology , Immunoglobulins/metabolism , Leukocytes/immunology , Animals , Autoantibodies/metabolism , Blister/immunology , Blister/pathology , Collagen Type VII/chemistry , Female , Granulocytes/immunology , Immunoglobulin G/metabolism , Immunoglobulins/chemistry , Mice , Mice, Inbred BALB C , Skin/pathologyABSTRACT
To enhance the efficiency of de visu or automatic detection and analysis of of the respiratory patterns, new techniques are introduced to process the respiratory signals. These techniques include: the dynamical frequency analysis, spectral envelope detection, three-dimensional representation of the spectral envelopes, and the 'respirogram'.
