BALB/c mice produce blister-causing antibodies upon immunization with a recombinant human desmoglein 3

JL Fan, O Memar, DJ McCormick… - The Journal of …, 1999 - journals.aai.org
JL Fan, O Memar, DJ McCormick, BS Prabhakar
The Journal of Immunology, 1999journals.aai.org
Pemphigus vulgaris (PV) is an Ab-mediated autoimmune blistering disease of mucotaneous
surfaces. Over 95% of the patients with PV express DR4 or DRw6, and the disease is
characterized by the presence of autoantibodies directed against desmoglein 3 (Dsg 3), a
protein expressed on keratinocytes. An appropriate animal model is required to understand
immunoregulation and to address the role of immunogenetic components in the production
of pathogenic Abs that are characteristic of PV. Therefore, we turned to the development of a …
Abstract
Pemphigus vulgaris (PV) is an Ab-mediated autoimmune blistering disease of mucotaneous surfaces. Over 95% of the patients with PV express DR4 or DRw6, and the disease is characterized by the presence of autoantibodies directed against desmoglein 3 (Dsg 3), a protein expressed on keratinocytes. An appropriate animal model is required to understand immunoregulation and to address the role of immunogenetic components in the production of pathogenic Abs that are characteristic of PV. Therefore, we turned to the development of a mouse model. Four strains of female mice (BALB/c, DBA/1, SJL/J, and HRS/J) were screened for their ability to produce pathogenic anti-Dsg 3 Abs. We demonstrated that only BALB/c mice immunized with a full-length Dsg 3 can produce pathogenic Abs capable of causing acantholysis of human foreskin in culture and blistering in neonatal mice. This observation suggested that either H-2 d or the BALB background contains the immunogenetic makeup necessary for the production of pathogenic anti-Dsg 3 Abs. No correlation was noted between a given isotype and the pathogenic potential of autoantibodies from different strains of mice. Similarly, the pattern of reactivity of Abs with a panel of 46 synthetic peptides that span the entire Dsg 3 failed to reveal any association between binding specificity and the pathogenic potential, and suggested that pathogenic Abs might recognize conformational epitopes. Moreover, our studies showed that the epitopes recognized by pathogenic Abs are contained within the extracellular Dsg 3.
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