NDLI: Blocking Fc receptor I on granulocytes prevents tissue damage induced by IgA autoantibodies.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kirtschig, Gudula Sitaru, Cassian Van Egmond, Marjolein Florea, Florina Hage, J. Joris Sesarman, Alina Bakema, Jantine E. Tuk, Cornelis W. Van Der Steen, Lydia P.
Description	Country affiliation: Netherlands Author Affiliation: van der Steen LP ( Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.)
Abstract	IgA represents the most prominent Ab class at mucosal surfaces and the second most prevalent Ab in human blood after IgG. We recently demonstrated that cross-linking of the granulocyte IgA FcR (Fc RI) by IgA induces a chemotactic-driven positive-feedback migration loop, hereby amplifying recruitment of granulocytes to IgA deposits. Therefore, we postulated that aberrant IgA-Ag complexes, which can be found in tissues in IgA-mediated diseases, are responsible for tissue damage by inducing continuous granulocyte migration and activation. Using an IgA-dependent skin-blistering disease as a model system, we demonstrated colocalization of Fc RI-positive granulocyte infiltrates with IgA in cryosections of lesional skin of patients suffering from this disease. Furthermore, we showed granulocyte migration to IgA deposits injected in human skin explants and in murine skin of Fc RI transgenic mice in vivo. Importantly, ex vivo migration and tissue damage were inhibited by blocking Fc RI, indicating that these events are dependent on the interaction of IgA autoantibodies with Fc RI. Thus, interrupting the granulocyte migration loop by blocking Fc RI reduces tissue damage in diseases with aberrant IgA-immune complexes. As such, our results may lead to development of new therapies for IgA-mediated chronic inflammatory diseases, hereby decreasing severe morbidity and improving quality of life for these patients.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoantibodies Immunology Autoimmune Diseases Granulocytes Immunoglobulin A Receptors, Igg Animals Metabolism Chemotaxis, Leukocyte Enzyme-linked Immunosorbent Assay Fluorescent Antibody Technique Immunohistochemistry Mice Mice, Transgenic Skin Diseases, Vesiculobullous Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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