TY - JOUR
T1 - IgG4 Autoantibodies in Organ-Specific Autoimmunopathies
T2 - Reviewing Class Switching, Antibody-Producing Cells, and Specific Immunotherapies
AU - Koneczny, Inga
AU - Tzartos, John
AU - Mané-Damas, Marina
AU - Yilmaz, Vuslat
AU - Huijbers, Maartje G
AU - Lazaridis, Konstantinos
AU - Höftberger, Romana
AU - Tüzün, Erdem
AU - Martinez-Martinez, Pilar
AU - Tzartos, Socrates
AU - Leypoldt, Frank
N1 - Copyright © 2022 Koneczny, Tzartos, Mané-Damas, Yilmaz, Huijbers, Lazaridis, Höftberger, Tüzün, Martinez-Martinez, Tzartos and Leypoldt.
PY - 2022/3/24
Y1 - 2022/3/24
N2 - Organ-specific autoimmunity is often characterized by autoantibodies targeting proteins expressed in the affected tissue. A subgroup of autoimmunopathies has recently emerged that is characterized by predominant autoantibodies of the IgG4 subclass (IgG4-autoimmune diseases; IgG4-AID). This group includes pemphigus vulgaris, thrombotic thrombocytopenic purpura, subtypes of autoimmune encephalitis, inflammatory neuropathies, myasthenia gravis and membranous nephropathy. Although the associated autoantibodies target specific antigens in different organs and thus cause diverse syndromes and diseases, they share surprising similarities in genetic predisposition, disease mechanisms, clinical course and response to therapies. IgG4-AID appear to be distinct from another group of rare immune diseases associated with IgG4, which are the IgG4-related diseases (IgG4-RLD), such as IgG4-related which have distinct clinical and serological properties and are not characterized by antigen-specific IgG4. Importantly, IgG4-AID differ significantly from diseases associated with IgG1 autoantibodies targeting the same organ. This may be due to the unique functional characteristics of IgG4 autoantibodies (e.g. anti-inflammatory and functionally monovalent) that affect how the antibodies cause disease, and the differential response to immunotherapies of the IgG4 producing B cells/plasmablasts. These clinical and pathophysiological clues give important insight in the immunopathogenesis of IgG4-AID. Understanding IgG4 immunobiology is a key step towards the development of novel, IgG4 specific treatments. In this review we therefore summarize current knowledge on IgG4 regulation, the relevance of class switching in the context of health and disease, describe the cellular mechanisms involved in IgG4 production and provide an overview of treatment responses in IgG4-AID.
AB - Organ-specific autoimmunity is often characterized by autoantibodies targeting proteins expressed in the affected tissue. A subgroup of autoimmunopathies has recently emerged that is characterized by predominant autoantibodies of the IgG4 subclass (IgG4-autoimmune diseases; IgG4-AID). This group includes pemphigus vulgaris, thrombotic thrombocytopenic purpura, subtypes of autoimmune encephalitis, inflammatory neuropathies, myasthenia gravis and membranous nephropathy. Although the associated autoantibodies target specific antigens in different organs and thus cause diverse syndromes and diseases, they share surprising similarities in genetic predisposition, disease mechanisms, clinical course and response to therapies. IgG4-AID appear to be distinct from another group of rare immune diseases associated with IgG4, which are the IgG4-related diseases (IgG4-RLD), such as IgG4-related which have distinct clinical and serological properties and are not characterized by antigen-specific IgG4. Importantly, IgG4-AID differ significantly from diseases associated with IgG1 autoantibodies targeting the same organ. This may be due to the unique functional characteristics of IgG4 autoantibodies (e.g. anti-inflammatory and functionally monovalent) that affect how the antibodies cause disease, and the differential response to immunotherapies of the IgG4 producing B cells/plasmablasts. These clinical and pathophysiological clues give important insight in the immunopathogenesis of IgG4-AID. Understanding IgG4 immunobiology is a key step towards the development of novel, IgG4 specific treatments. In this review we therefore summarize current knowledge on IgG4 regulation, the relevance of class switching in the context of health and disease, describe the cellular mechanisms involved in IgG4 production and provide an overview of treatment responses in IgG4-AID.
KW - Autoantibodies
KW - B-Lymphocytes
KW - Humans
KW - Immunoglobulin Class Switching
KW - Immunoglobulin G
KW - Immunotherapy
KW - Myasthenia Gravis
KW - Fab-arm exchange
KW - FC-GAMMA-RIII
KW - REGULATORY B-CELLS
KW - IL-4
KW - MHC
KW - INFLAMMATORY DEMYELINATING POLYNEUROPATHY
KW - THROMBOTIC THROMBOCYTOPENIC PURPURA
KW - POSITIVE MYASTHENIA-GRAVIS
KW - memory B cells
KW - IgG4 autoimmune disease
KW - IL-10
KW - HUMAN-IMMUNOGLOBULIN-G
KW - PEMPHIGUS-VULGARIS
KW - PLASMA-EXCHANGE
KW - IN-VITRO
KW - autoimmunity
KW - INTRAVENOUS IMMUNOGLOBULIN
U2 - 10.3389/fimmu.2022.834342
DO - 10.3389/fimmu.2022.834342
M3 - (Systematic) Review article
C2 - 35401530
SN - 1664-3224
VL - 13
SP - 834342
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 834342
ER -