caa a22 4500 475748107 CHVBK 20180406123519.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1023/A:1026451530967 doi (NATIONALLICENCE)springer-10.1023/A:1026451530967 Autoantibodies to Type VII Collagen Have Heterogeneous Subclass and Light Chain Compositions and Their Complement-Activating Capacities Do Not Correlate with the Inflammatory Clinical Phenotype [Elektronische Daten] [Kavitha Gandhi, Mei Chen, Sumaira Aasi, Jean-Christophe Lapiere, David Woodley, Lawrence Chan] Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are blistering skin diseases characterized by IgG autoantibodies that predominantly target the noncollagenous domain 1 of type VII collagen, a skin basement membrane component. The basic immunologic events leading to the blistering processes in these diseases remains unclear. We defined the subclass and light chain compositions of the IgG autoantibodies in 15 patients, in order to gain insight into the blistering mechanism. Immunofluorescence correlated the patients'in vivo-bound and circulating antibasement membrane autoantibodies. Four eukaryotic recombinant proteins, including one full-length and three truncated noncollagenous domain 1 proteins generated by sequential deletion of C-terminal amino acids, were used to perform enzyme-linked immunosorbent assay to detect the patients' anti-type VII collagen autoantibodies. The majority of patients' autoantibodies contained both complement-activating and non-complement-activating IgG subclasses. The presence or absence of complement-activating IgG autoantibody subclasses did not correlate with the inflammatory or noninflammatory clinical phenotype. The majority of tested sera contained both κ and λ light chain autoantibodies. All sera that reacted to the full-length noncollagenous domain 1 also reacted to the smallest truncated protein containing the cartilage matrix protein and the first three fibronectinlike repeats. The patients' anti-type VII collagen autoantibodies, likely to be polyclonal in nature, may contribute to the pathogenesis of the blistering process by both complement-dependent inflammatory injury and complement-independent mechanical disruption of the anchoring function of type VII collagen. The N-terminal region of the noncollagenous domain 1 may contain an important antigenic epitope targeted by the IgG autoantibodies. Plenum Publishing Corporation, 2000 Autoantibodies nationallicence subclass nationallicence light chain nationallicence epidermolysis bullosa acquisita nationallicence epitope nationallicence Gandhi Kavitha Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut Chen Mei Division of Dermatology, University of Southern California School of Medicine, Los Angeles, California aut Aasi Sumaira Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut Lapiere Jean-Christophe Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut Woodley David Division of Dermatology, University of Southern California School of Medicine, Los Angeles, California aut Chan Lawrence Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut Journal of Clinical Immunology Kluwer Academic Publishers-Plenum Publishers 20/6(2000-11-01), 416-423 0271-9142 20:6<416 2000 20 10875 https://doi.org/10.1023/A:1026451530967 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1026451530967 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gandhi Kavitha Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut NATIONALLICENCE 700 1- Chen Mei Division of Dermatology, University of Southern California School of Medicine, Los Angeles, California aut NATIONALLICENCE 700 1- Aasi Sumaira Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut NATIONALLICENCE 700 1- Lapiere Jean-Christophe Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut NATIONALLICENCE 700 1- Woodley David Division of Dermatology, University of Southern California School of Medicine, Los Angeles, California aut NATIONALLICENCE 700 1- Chan Lawrence Department of Dermatology, Northwestern University Medical School, Chicago, Illinois aut NATIONALLICENCE 773 0- Journal of Clinical Immunology Kluwer Academic Publishers-Plenum Publishers 20/6(2000-11-01), 416-423 0271-9142 20:6<416 2000 20 10875 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer