TY - JOUR
T1 - The unique properties of IgG4 and its roles in health and disease
AU - Rispens, Theo
AU - Huijbers, Maartje G.
N1 - Funding Information: M.G.H. thanks the neuroimmunology research group, J. Verschuuren, J. Plomp and S. van der Maarel for fruitful discussions on IgG4. T.R. thanks M. van Ham, A. ten Brinke, J. Koers, P. P. Unger and R. Aalberse for inspiring discussions on IgG4. M.G.H and T.R. gratefully acknowledge the Target-to-B (T2B) consortium for supporting their work on IgG4. Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023/11
Y1 - 2023/11
N2 - IgG4 is the least abundant subclass of IgG in human serum and has unique functional features. IgG4 is largely unable to activate antibody-dependent immune effector responses and, furthermore, undergoes Fab (fragment antigen binding)-arm exchange, rendering it bispecific for antigen binding and functionally monovalent. These properties of IgG4 have a blocking effect, either on the immune response or on the target protein of IgG4. In this Review, we discuss the unique structural characteristics of IgG4 and how these contribute to its roles in health and disease. We highlight how, depending on the setting, IgG4 responses can be beneficial (for example, in responses to allergens or parasites) or detrimental (for example, in autoimmune diseases, in antitumour responses and in anti-biologic responses). The development of novel models for studying IgG4 (patho)physiology and understanding how IgG4 responses are regulated could offer insights into novel treatment strategies for these IgG4-associated disease settings.
AB - IgG4 is the least abundant subclass of IgG in human serum and has unique functional features. IgG4 is largely unable to activate antibody-dependent immune effector responses and, furthermore, undergoes Fab (fragment antigen binding)-arm exchange, rendering it bispecific for antigen binding and functionally monovalent. These properties of IgG4 have a blocking effect, either on the immune response or on the target protein of IgG4. In this Review, we discuss the unique structural characteristics of IgG4 and how these contribute to its roles in health and disease. We highlight how, depending on the setting, IgG4 responses can be beneficial (for example, in responses to allergens or parasites) or detrimental (for example, in autoimmune diseases, in antitumour responses and in anti-biologic responses). The development of novel models for studying IgG4 (patho)physiology and understanding how IgG4 responses are regulated could offer insights into novel treatment strategies for these IgG4-associated disease settings.
UR - http://www.scopus.com/inward/record.url?scp=85153340449&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41577-023-00871-z
DO - https://doi.org/10.1038/s41577-023-00871-z
M3 - Review article
C2 - 37095254
SN - 1474-1733
VL - 23
SP - 763
EP - 778
JO - Nature Reviews. Immunology
JF - Nature Reviews. Immunology
IS - 11
ER -