% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Hudemann:169841,
author = {C. Hudemann and R. Maglie and M. Llamazares$^*$ and B.
Beckert and D. Didona and R. Tikkanen and T. Schmitt and T.
Hashimoto and J. Waschke and M. Hertl and R. Eming},
title = {{H}uman desmocollin 3-specific {I}g{G} antibodies are
pathogenic in a humanized {HLA}-class {II} transgenic mouse
model of pemphigus.},
journal = {The journal of investigative dermatology},
volume = {142},
number = {3, Part B},
issn = {0022-202X},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {DKFZ-2021-01584},
pages = {915-923.e3},
year = {2022},
note = {Volume 142, Issue 3, Part B, March 2022, Pages 915-923.e3},
abstract = {Pemphigus is a potentially lethal autoimmune bullous skin
disorder, which is associated with IgG autoantibodies
against desmoglein 3 (Dsg3) and Dsg1. Notably, a subset of
pemphigus patients presents with a similar clinical
phenotype in the absence of anti-Dsg IgG, suggesting the
presence of serum IgG reactive with desmosomal components
other than Dsg1 or Dsg3. We and others have previously shown
that such patients have serum IgG autoantibodies against
desmocollin 3 (Dsc3), a component of desmosomes, that induce
loss of keratinocyte adhesion ex vivo. Moreover, Dsc3
hypomorphic mice show a severe blistering phenotype of the
mucous membrane which is highly characteristic in pemphigus.
These findings prompted us to study induction and regulation
of anti-human Dsc3 IgG in humanized mice transgenic for
HLA-DRB1*04:02, which is a highly prevalent haplotype in
pemphigus. We show that IgG from sera of immunized mice
induce acantholysis in a dispase-based keratinocyte
dissociation assay via the activation of p38
mitogen-activated protein kinases and epidermal growth
factor receptor. Passive IgG transfer from mice immunized
with recombinant human Dsc3 into neonates did not induce
intraepidermal loss of adhesion presumably due to the lack
of homology between human and mouse Dsc3. Ex vivo
stimulation of splenocytes from Dsc3-immunized mice with
human Dsc3 leads to a significant proliferative
interferon-γ and interleukin 4 T cell response, which is
restricted by HLA-DR/DQ. These findings suggest that
induction of pathogenic anti-Dsc3 IgG is associated with
Dsc3-specific T cells that recognize Dsc3 in association
with HLA-DRB1*04:02.},
keywords = {HLA (Other) / antibodies (Other) / autoimmunity (Other) /
desmocollin (Other) / pemphigus vulgaris (Other)},
cin = {B370},
ddc = {610},
cid = {I:(DE-He78)B370-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34265330},
doi = {10.1016/j.jid.2021.06.017},
url = {https://inrepo02.dkfz.de/record/169841},
}