Generation of antibodies of distinct subclasses and specificity is linked to H2s in an active mouse model of epidermolysis bullosa acquisita.

Abstract

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease, characterized by antibodies to type VII collagen (COL7). EBA can be induced in mice by immunization with a fragment of the non-collagenous 1 domain of murine COL7. Contrary to other autoimmune diseases, e.g., rheumatoid arthritis, little is known about the genetic susceptibility for EBA. We therefore used the EBA mouse model to address the hypothesis that disease induction depends on the major histocompatibility complex (MHC) haplotype. Mice from different inbred strains were immunized with recombinant murine COL7. Five distinct responses were observed: induction of (i) severe disease in SJL/J (H2s) and female MRL/MpJ (H2k), (ii) mild and transient disease in C57Bl/10.s (H2s), (iii) microscopic blistering in DBA/1J (H2q), (iv) only presence of non-pathogenic autoantibodies in C57Bl/6J (H2b), NZM2410/J (H2z), BXD2 (H2b), and male MRL/MpJ, and (v) complete resistance to EBA in NOD/ShiLtJ (H2g7) and C57Bl/10.q (H2q) mice. Overall, susceptibility to EBA was strongly associated with H2s. In addition, the diseased phenotype was associated with autoantibodies to specific regions of COL7. Our findings show that induction of antibodies with a distinct specificity is linked to the MHC haplotype in experimental EBA. Furthermore, our data are the basis for future studies with the goal of identifying non-MHC EBA susceptibility genes.

• Authors: Ralf J Ludwig, Andreas Recke, Katja Bieber, Susen Müller, Andreia de Castro Marques, David Banczyk, Misa Hirose, Michael Kasperkiewicz, Norito Ishii, Enno Schmidt, Jürgen Westermann, Detlef Zillikens, Saleh M Ibrahim
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 131 Issue 1 Pg. 167-76 (Jan 2011) ISSN: 1523-1747 [Electronic] United States
• PMID: 20720563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Collagen Type VII
• Epitopes

Topics

• Animals
• Antibody Specificity
• Autoantibodies (blood, classification, immunology)
• Blister (genetics, immunology)
• Collagen Type VII (chemistry, immunology)
• Complement Fixation Tests
• Disease Models, Animal
• Epidermolysis Bullosa Acquisita (genetics, immunology)
• Epitopes (immunology)
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Immune Tolerance (immunology)
• Major Histocompatibility Complex (genetics, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Inbred MRL lpr
• Protein Structure, Tertiary
• Species Specificity