Immunization-induced EBA
Experimental EBA can also be induced in susceptible mouse strains by either single (J Invest Dermatol, 2010) or repetative (J Immunol, 2006) immunization with an immunodominant fragment located within type VII collagen NC1 domain. Disease induction requires:
- T cells ( J Immunol, 2010)
- MHC haplotype (J Invest Dermatol, 2010)
- Th1 polarization (J Immunol, 2011)
- non-MHC genes (J Invest Dermatol, 2012)
- CD4+ T cells (J Immunol, 2013)
- APC (B cells, dendritic cells, and macrophages, J Immunol, 2013)
- GM-CSF (J Immunol, 2014)
- Diverstiy of the skin mircobiome (J Autoimmun, 2016)
The following therapeutic interventions lead to disease improvement:
HSP90 inhibition (Blood, 2011)
- Enzymatic autoantibody glycan hydrolysis (EndoS) (J Autoimmun, 2012)
- IVIG (J Invest Dermatol, 2015)
- sCD32 / SM101 (J Invest Dermatol, 2015)
- Corticosteroids (J Invest Dermatol, 2015)
- Dimethylfumarate (J Invest Dermatol, 2015)
- PDE4 inhibition (J Invest Dermatol, 2016)
- topical HSP90 inhibition (J Invest Dermatol, 2017)
- Calcitriol (J Invest Dermatol, 2018)
Antibody transfer model of EBA
An antibody-transfer of epidermolysis bullosa acquisita (EBA) was originally developed in 2005 (J Clin Invest, 2005). The disease is induced by repetetive injections of rabbit anti-mouse type VII antibodies into susceptible adult mouse strains. Within 2-4 days skin lesions develop. In addition to skin lesions, tissue injury is also induced throughout the entire gut (J Pathol, 2011).
Overall, this model is ideally suited to investigate autoantibody-induced tissue injury in vivo. Induction of clinical skin lesion depends on:
- neutrophils (J Pathol, 2007)
- reactive oxygen species (J Pathol, 2007)
- adhesion molecules; e.g. CD18 (J Pathol, 2007)
- complement activation (J Immunol, 2007)
- Fc gamma receptors (J Clin Invest, 2005)
- PI3K beta signaling (Sci Signal, 2011)
- Fc gamma receptor 4 (J Pathol, 2012)
- PROTECTIVE role of IL-6 and IL-1ra (J Autoimmun, 2013)
- p38 MAPK, AKT, ERK1/2 signaling (J Invest Dermatol, 2013)
- GM-CSF (J Immunol, 2014)
- Flightless I (J Pathol, 2014)
- Scr kinases (J Exp Med, 2014)
- IL-1 (J Immunol, 2015)
- RORa (J Pathol, 2015)
- mouse strain (J Pathol, 2015)
- γδ- and NK T cells (Sci Rep, 2016)
- inhibited by IL-10 (JACI, 2016)
- CARD9 (Nat Commun, 2016)
- inhibited by Treg (Front Immunol, 2017)
- LTB4 (J Invest Dermatol, 2017)
- TNFα (Mol Med, 2017)
- SYK (Front Immunol, 2018 and J Invest Dermatol, 2017)
Key references
Immunization-induced EBA
B cells, dendritic cells, and macrophages are required to induce an autoreactive CD4 helper T cell response in experimental epidermolysis bullosa acquisita (PDF). J Immunol. 2013
Generation of antibodies of distinct subclasses and specificity is linked to H2s in an active mouse model of epidermolysis bullosa acquisita (PDF). J Invest Dermatol. 2011
Induction of complement-fixing autoantibodies against type VII collagen results in subepidermal blistering in mice (PDF). J Immunol. 2006
Antibody transfer-induced EBA
Regulatory T cells suppress inflammation and blistering in pemphigoid diseases (PDF). Front Immunol. 2017
Radiosensitive hematopoietic cells determine the extent of skin inflammation in experimental epidermolysis bullosa acquisita (PDF). J Immunol. 2015
Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen (PDF). J Clin Invest. 2005
