121 Pharmacological inhibition of the neonatal Fc receptor reduces disease activity in an antibody transfer-induced model of bullous pemphigoid
نویسندگان
چکیده
Bullous pemphigoid (BP) is the most common autoimmune blistering disease driven by autoantibodies targeting type XVII collagen (Col17, BP180), which mediates adhesion of basal keratinocytes to underlying basement membrane in epithelial tissues. Here, we evaluated therapeutic effects murine Fc fragment IgG2c-ABDEG (mABDEG), a derivative neonatal receptor (FcRn) inhibitor efgartigimod, experimental BP. mABDEG targets FcRn, plays crucial role homeostasis endogenous IgG, resulting reduced levels circulating IgG including autoantibodies. BP was induced C57BL6/J mice subcutaneous injections rabbit anti-murine Col17 every other day. or isotype control were administered intraperitoneally three days. mABDEG-treated presented with lower anti-Col17 serum from Day 6 throughout 12 (p < 0.05) and significant reduction affected body surface area compared control-treated on 0.001). This paralleled tissue-bound = C3 binding (p< 0.01) perilesional skin treatment vs. group. Moreover, lesional biopsies mABDEG- showed evidence for significantly less inflammation, particularly characterized strongly decreased frequencies neutrophils. Our data demonstrate that pharmacological inhibition FcRn represents promising strategy supports ongoing randomized controlled clinical trial evaluation antagonists
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.122