Exploring the depths of IgG4: insights into autoimmunity and novel treatments.

Autor:	Ünlü S; Koç University Research Center for Translational Medicine (KUTTAM), İstanbul, Türkiye.; Koç University School of Medicine, Istanbul, Türkiye., Sánchez Navarro BG; Department of Neurology with Experimental Neurology, Integrated Myasthenia Gravis Center, Neuroscience Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany., Cakan E; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States., Berchtold D; Department of Neurology with Experimental Neurology, Integrated Myasthenia Gravis Center, Neuroscience Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany., Meleka Hanna R; Department of Neurology with Experimental Neurology, Integrated Myasthenia Gravis Center, Neuroscience Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany., Vural S; Koç University Research Center for Translational Medicine (KUTTAM), İstanbul, Türkiye.; Department of Dermatology and Venereology, Koç University School of Medicine, İstanbul, Türkiye., Vural A; Koç University Research Center for Translational Medicine (KUTTAM), İstanbul, Türkiye.; Department of Neurology, Koç University School of Medicine, İstanbul, Türkiye., Meisel A; Department of Neurology with Experimental Neurology, Integrated Myasthenia Gravis Center, Neuroscience Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany., Fichtner ML; Koç University Research Center for Translational Medicine (KUTTAM), İstanbul, Türkiye.; Department of Neurology with Experimental Neurology, Integrated Myasthenia Gravis Center, Neuroscience Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Apr 18; Vol. 15, pp. 1346671. Date of Electronic Publication: 2024 Apr 18 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1346671
Abstrakt:	IgG4 subclass antibodies represent the rarest subclass of IgG antibodies, comprising only 3-5% of antibodies circulating in the bloodstream. These antibodies possess unique structural features, notably their ability to undergo a process known as fragment-antigen binding (Fab)-arm exchange, wherein they exchange half-molecules with other IgG4 antibodies. Functionally, IgG4 antibodies primarily block and exert immunomodulatory effects, particularly in the context of IgE isotype-mediated hypersensitivity reactions. In the context of disease, IgG4 antibodies are prominently observed in various autoimmune diseases combined under the term IgG4 autoimmune diseases (IgG4-AID). These diseases include myasthenia gravis (MG) with autoantibodies against muscle-specific tyrosine kinase (MuSK), nodo-paranodopathies with autoantibodies against paranodal and nodal proteins, pemphigus vulgaris and foliaceus with antibodies against desmoglein and encephalitis with antibodies against LGI1/CASPR2. Additionally, IgG4 antibodies are a prominent feature in the rare entity of IgG4 related disease (IgG4-RD). Intriguingly, both IgG4-AID and IgG4-RD demonstrate a remarkable responsiveness to anti-CD20-mediated B cell depletion therapy (BCDT), suggesting shared underlying immunopathologies. This review aims to provide a comprehensive exploration of B cells, antibody subclasses, and their general properties before examining the distinctive characteristics of IgG4 subclass antibodies in the context of health, IgG4-AID and IgG4-RD. Furthermore, we will examine potential therapeutic strategies for these conditions, with a special focus on leveraging insights gained from anti-CD20-mediated BCDT. Through this analysis, we aim to enhance our understanding of the pathogenesis of IgG4-mediated diseases and identify promising possibilities for targeted therapeutic intervention. Competing Interests: MF has further received speaker honoraria from Alexion Pharmaceuticals and is a member of the Alexion-Akademie based in Germany. AM has received speaker or consultancy honoraria or financial research support (paid to his institution) from Alexion Pharmaceuticals, argenx, Axunio, Desitin, Grifols, Hormosan Pharma, Janssen, Merck, Octapharma, UCB, and Xcenda. He serves as medical advisory board chairman of the German Myasthenia Gravis Society. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Ünlü, Sánchez Navarro, Cakan, Berchtold, Meleka Hanna, Vural, Vural, Meisel and Fichtner.)
Databáze:	MEDLINE
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