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

Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus ar e blistering skin diseases characterized by IgG autoantibodies that predomi nantly target the noncollagenous domain 1 of type VII collagen, a skin base ment membrane component. The basic immunologic events leading to the bliste ring processes in these diseases remains unclear. We defined the subclass a nd light chain compositions of the IgG autoantibodies in 15 patients, in or der to gain insight into the blistering mechanism. Immunofluorescence corre lated the patients' in vivo-bound and circulating antibasement membrane aut oantibodies. Four eukaryotic recombinant proteins, including one full-lengt h and three truncated noncollagenous domain 1 proteins generated by sequent ial deletion of C-terminal amino acids, were used to perform enzyme-linked immunosorbent assay to detect the patients' anti-type VII collagen autoanti bodies. The majority of patients' autoantibodies contained both complement- activating and non-complement-activating IgG subclasses. The presence or ab sence of complement-activating IgG autoantibody subclasses did not correlat e with the inflammatory or non-inflammatory clinical phenotype. The majorit y of tested sera contained both kappa and lambda light chain autoantibodies . All sera that reacted to the full-length noncollagenous domain 1 also rea cted to the smallest truncated protein containing the cartilage matrix prot ein and the first three fibronectinlike repeats. The patients' anti-type VI I collagen autoantibodies, likely to be polyclonal in nature, may contribut e to the pathogenesis of the blistering process by both complement-dependen t inflammatory injury and complement-independent mechanical disruption of t he anchoring function of type Vn collagen. The N-terminal region of the non collagenous domain 1 may contain an important antigenic epitope targeted by the IgG autoantibodies.