TY - JOUR
T1 - The relevance of the IgG subclass of autoantibodies for blister induction in autoimmune bullous skin diseases
AU - Sitaru, Cassian
AU - Mihai, Sidonia
AU - Zillikens, Detlef
N1 - Funding Information:
Acknowledgments This work was supported by grants from the Deutsche Forschungsgemeinschaft (Zi 439/6-2 and SI 1281/1-1) and Else-Kröner-Fresenius-Stiftung (P30-06//A24/06).
PY - 2007/4
Y1 - 2007/4
N2 - Autoimmune bullous skin diseases are characterized by autoantibodies and T cells specific to structural proteins maintaining cell-cell and cell-matrix adhesion in the skin. Existing clinical and experimental evidence generally supports a pathogenic role of autoantibodies for blister formation. These autoantibodies belong to several IgG subclasses, which associate with different functional properties and may thus determine the pathogenic potential of IgG antibodies. In pemphigus diseases, binding of IgG to keratinocytes is sufficient to cause intraepidermal blisters without engaging innate immune effectors and IgG4 autoantibodies seem to mainly mediate acantholysis. In contrast, in most subepidermal autoimmune blistering diseases, complement activation and recruitment and activation of leukocytes by autoantibodies are required for blister induction. In these conditions, tissue damage is thought to be mainly mediated by IgG1, but not IgG4 autoantibodies. This review summarizes the current knowledge on the pathogenic relevance of the IgG subclass of autoantibodies for blister formation. Characterization of the pathogenically relevant subclass(es) of autoantibodies not only provides mechanistic insights, but should greatly facilitate the development of improved therapeutic modalities of autoimmune blistering diseases.
AB - Autoimmune bullous skin diseases are characterized by autoantibodies and T cells specific to structural proteins maintaining cell-cell and cell-matrix adhesion in the skin. Existing clinical and experimental evidence generally supports a pathogenic role of autoantibodies for blister formation. These autoantibodies belong to several IgG subclasses, which associate with different functional properties and may thus determine the pathogenic potential of IgG antibodies. In pemphigus diseases, binding of IgG to keratinocytes is sufficient to cause intraepidermal blisters without engaging innate immune effectors and IgG4 autoantibodies seem to mainly mediate acantholysis. In contrast, in most subepidermal autoimmune blistering diseases, complement activation and recruitment and activation of leukocytes by autoantibodies are required for blister induction. In these conditions, tissue damage is thought to be mainly mediated by IgG1, but not IgG4 autoantibodies. This review summarizes the current knowledge on the pathogenic relevance of the IgG subclass of autoantibodies for blister formation. Characterization of the pathogenically relevant subclass(es) of autoantibodies not only provides mechanistic insights, but should greatly facilitate the development of improved therapeutic modalities of autoimmune blistering diseases.
UR - http://www.scopus.com/inward/record.url?scp=34248150428&partnerID=8YFLogxK
U2 - 10.1007/s00403-007-0734-0
DO - 10.1007/s00403-007-0734-0
M3 - Scientific review articles
C2 - 17277959
AN - SCOPUS:34248150428
SN - 0340-3696
VL - 299
SP - 1
EP - 8
JO - Archives of Dermatological Research
JF - Archives of Dermatological Research
IS - 1
ER -