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Effects of intravenous immunoglobulins on mice with experimental epidermolysis bullosa acquisita.

Abstract
Although well-designed prospective trials are generally lacking, intravenous immunoglobulins (IVIG) seem an effective adjuvant treatment for autoimmune bullous skin diseases. Here, efficacy of IVIG monotherapy was compared with corticosteroid treatment in mice with immunization-induced experimental epidermolysis bullosa acquisita (EBA), an autoimmune bullous skin disease characterized by autoantibodies against type VII collagen. We found that IVIG significantly ameliorated clinical disease severity and skin neutrophil infiltration compared with vehicle-treated mice, whereas methylprednisolone showed comparatively less pronounced effects. Efficacy of IVIG was accompanied by reduced levels of autoantibodies, a shift toward noncomplement-fixing autoantibodies, and lower complement deposition at the dermal-epidermal junction. In addition, peripheral Gr-1-positive cells of IVIG-treated animals showed reduced expression of the activating Fcγ receptor IV, which we recently described as a major mediator of tissue injury in experimental EBA. These data show that treatment with IVIG is superior to systemic corticosteroids in experimental EBA and that the effects of IVIG are pleiotropic involving modulation of both the adaptive and innate immune response, although the detailed mode of action of IVIG in this model remains in need of further elucidation.
AuthorsMisa Hirose, Benjamin Tiburzy, Norito Ishii, Elena Pipi, Sabina Wende, Ellen Rentz, Falk Nimmerjahn, Detlef Zillikens, Rudolf A Manz, Ralf J Ludwig, Michael Kasperkiewicz
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 135 Issue 3 Pg. 768-75 (Mar 2015) ISSN: 1523-1747 [Electronic] United States
PMID25330299 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenal Cortex Hormones
  • Autoantibodies
  • Collagen Type VII
  • Fcgr4 protein, mouse
  • Immunoglobulins, Intravenous
  • Receptors, Cell Surface
  • Receptors, IgG
  • granulocyte receptor 1, mouse
Topics
  • Adrenal Cortex Hormones (therapeutic use)
  • Animals
  • Autoantibodies (metabolism)
  • Collagen Type VII (immunology)
  • Disease Models, Animal
  • Epidermolysis Bullosa Acquisita (drug therapy, metabolism)
  • Immunoglobulins, Intravenous (therapeutic use)
  • Mice
  • Mice, Mutant Strains
  • Receptors, Cell Surface (metabolism)
  • Receptors, IgG (metabolism)
  • Severity of Illness Index
  • Treatment Outcome

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