TY - JOUR
T1 - Intravenous Ig Ameliorates Disease in a Murine Model of Anti–Laminin 332 Mucous Membrane Pemphigoid
AU - Murthy, Sripriya
AU - Patzelt, Sabrina
AU - Künstner, Axel
AU - Busch, Hauke
AU - Schmidt, Enno
AU - Sadik, Christian D.
N1 - Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2024
Y1 - 2024
N2 - Intravenous Ig (IVIg) is used to treat mucous membrane pemphigoid, although its therapeutic effectivity is not sufficiently supported by randomized controlled clinical trials, and its mode of action is only insufficiently understood. We have examined the effect of IVIg in a mouse model of anti–laminin 332 mucous membrane pemphigoid and found that IVIg ameliorates both cutaneous and mucosal inflammatory lesions. Our investigation into the modes of action of IVIg in mucous membrane pemphigoid indicated effective anti-inflammatory mechanisms beyond the enhanced degradation of IgG mediated through inhibition of the FcRn. Our results suggest that IVIg curbs the activation of neutrophils at several levels. This includes a direct, immediate inhibitory effect on neutrophil activation by immune complexes but not C5a, which blunts the release of ROS and leukotriene B4 from neutrophils. IVIg also suppresses the formation of neutrophil extracellular traps in response to calcium ion ionophore. In vivo treatment with IVIg altered the transcriptome of blood leukocytes and bone marrow neutrophils toward less proinflammatory phenotypes. Collectively, our results support the effectivity of IVIg in the treatment of mucous membrane pemphigoid and indicate that effects on neutrophils at multiple levels may significantly contribute to its therapeutic effects.
AB - Intravenous Ig (IVIg) is used to treat mucous membrane pemphigoid, although its therapeutic effectivity is not sufficiently supported by randomized controlled clinical trials, and its mode of action is only insufficiently understood. We have examined the effect of IVIg in a mouse model of anti–laminin 332 mucous membrane pemphigoid and found that IVIg ameliorates both cutaneous and mucosal inflammatory lesions. Our investigation into the modes of action of IVIg in mucous membrane pemphigoid indicated effective anti-inflammatory mechanisms beyond the enhanced degradation of IgG mediated through inhibition of the FcRn. Our results suggest that IVIg curbs the activation of neutrophils at several levels. This includes a direct, immediate inhibitory effect on neutrophil activation by immune complexes but not C5a, which blunts the release of ROS and leukotriene B4 from neutrophils. IVIg also suppresses the formation of neutrophil extracellular traps in response to calcium ion ionophore. In vivo treatment with IVIg altered the transcriptome of blood leukocytes and bone marrow neutrophils toward less proinflammatory phenotypes. Collectively, our results support the effectivity of IVIg in the treatment of mucous membrane pemphigoid and indicate that effects on neutrophils at multiple levels may significantly contribute to its therapeutic effects.
UR - http://www.scopus.com/inward/record.url?scp=85194169090&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/03c4d4d9-1194-3aa0-b1ff-4853a799b701/
U2 - 10.1016/j.jid.2024.02.038
DO - 10.1016/j.jid.2024.02.038
M3 - Journal articles
C2 - 38692406
AN - SCOPUS:85194169090
SN - 0022-202X
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -