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IgG4-related disease and its pathogenesis-cross-talk between innate and acquired immunity.

Umehara H, Nakajima A, Nakamura T, Kawanami T, Tanaka M, Dong L, Kawano M - Int. Immunol. (2014)

Bottom Line: IgG4-related disease (IgG4-RD) is a novel clinical entity proposed in Japan in the 21th century and is attracting strong attention over the world.The characteristic manifestations of IgG4-RD are increased serum IgG4 concentration and tumefaction by IgG4(+) plasma cells.Recently, many reports of aberrant acquired immunity such as Th2-diminated immune responses have been published.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan Department of Clinical Immunology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan Present address: Department of Clinical Immunology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan umehara606@gmail.com.

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Structural characteristics of IgG4 (51). Generally, each immunoglobulin monomer consists of two identical half-molecules; two such monomers recognizing different antigens are shown in pink or green at the top of the figure. Each half-molecule is a pair of a heavy chain (H strand) and a light chain (L chain). Two pairs are generally joined together by the non-covalent bond of the 3C domain and the covalent bond of the hinge segment. However, because IgG4 does not have a covalent bond between H strands and the covalent bond is carried out within the H strand, a characteristic space structure is taken. The important features of IgG4 are functional monovalency and half-molecule exchange. IgG4 antibodies may exist as pairs of different half-molecules (functional monovalency) by the intra-heavy-chain disulfide-bonded structure. Under certain conditions, IgG4-Fabs may join together, making a chimeric antibody by the inter-heavy-chain disulfide bonds. Therefore, IgG4 may decrease or neutralize the cellular immunity triggered by IgG1.
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Figure 3: Structural characteristics of IgG4 (51). Generally, each immunoglobulin monomer consists of two identical half-molecules; two such monomers recognizing different antigens are shown in pink or green at the top of the figure. Each half-molecule is a pair of a heavy chain (H strand) and a light chain (L chain). Two pairs are generally joined together by the non-covalent bond of the 3C domain and the covalent bond of the hinge segment. However, because IgG4 does not have a covalent bond between H strands and the covalent bond is carried out within the H strand, a characteristic space structure is taken. The important features of IgG4 are functional monovalency and half-molecule exchange. IgG4 antibodies may exist as pairs of different half-molecules (functional monovalency) by the intra-heavy-chain disulfide-bonded structure. Under certain conditions, IgG4-Fabs may join together, making a chimeric antibody by the inter-heavy-chain disulfide bonds. Therefore, IgG4 may decrease or neutralize the cellular immunity triggered by IgG1.

Mentions: Among the four subclasses of IgGs, the most abundant IgG is IgG1 ranging from 5 to 11mg ml-1, whereas the least abundant subclass is IgG4 ranging from 0.35 to 0.51mg ml-1 (51). The important differences between IgG1 and IgG4 are a few amino acid differences in the CH2 domain, CPSC and CPPC (P, proline; S, serine; C, cysteine) for IgG4 and IgG1 core hinge lesions, respectively. The S228 in IgG4 results in a more flexible hinge enabling the formation of an intrachain cyclized disulfide and leads to the appearance of half-antibodies, which contain non-covalently linked heavy chains as determined by analysis of IgG4 antibodies under denaturing conditions (51, 52). Thus, IgG4 antibodies can exchange Fab arms by swapping a heavy chain and attached light chain and form bispecific antibodies that function as monovalent molecules (Fig. 3) (51, 53).


IgG4-related disease and its pathogenesis-cross-talk between innate and acquired immunity.

Umehara H, Nakajima A, Nakamura T, Kawanami T, Tanaka M, Dong L, Kawano M - Int. Immunol. (2014)

Structural characteristics of IgG4 (51). Generally, each immunoglobulin monomer consists of two identical half-molecules; two such monomers recognizing different antigens are shown in pink or green at the top of the figure. Each half-molecule is a pair of a heavy chain (H strand) and a light chain (L chain). Two pairs are generally joined together by the non-covalent bond of the 3C domain and the covalent bond of the hinge segment. However, because IgG4 does not have a covalent bond between H strands and the covalent bond is carried out within the H strand, a characteristic space structure is taken. The important features of IgG4 are functional monovalency and half-molecule exchange. IgG4 antibodies may exist as pairs of different half-molecules (functional monovalency) by the intra-heavy-chain disulfide-bonded structure. Under certain conditions, IgG4-Fabs may join together, making a chimeric antibody by the inter-heavy-chain disulfide bonds. Therefore, IgG4 may decrease or neutralize the cellular immunity triggered by IgG1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4201844&req=5

Figure 3: Structural characteristics of IgG4 (51). Generally, each immunoglobulin monomer consists of two identical half-molecules; two such monomers recognizing different antigens are shown in pink or green at the top of the figure. Each half-molecule is a pair of a heavy chain (H strand) and a light chain (L chain). Two pairs are generally joined together by the non-covalent bond of the 3C domain and the covalent bond of the hinge segment. However, because IgG4 does not have a covalent bond between H strands and the covalent bond is carried out within the H strand, a characteristic space structure is taken. The important features of IgG4 are functional monovalency and half-molecule exchange. IgG4 antibodies may exist as pairs of different half-molecules (functional monovalency) by the intra-heavy-chain disulfide-bonded structure. Under certain conditions, IgG4-Fabs may join together, making a chimeric antibody by the inter-heavy-chain disulfide bonds. Therefore, IgG4 may decrease or neutralize the cellular immunity triggered by IgG1.
Mentions: Among the four subclasses of IgGs, the most abundant IgG is IgG1 ranging from 5 to 11mg ml-1, whereas the least abundant subclass is IgG4 ranging from 0.35 to 0.51mg ml-1 (51). The important differences between IgG1 and IgG4 are a few amino acid differences in the CH2 domain, CPSC and CPPC (P, proline; S, serine; C, cysteine) for IgG4 and IgG1 core hinge lesions, respectively. The S228 in IgG4 results in a more flexible hinge enabling the formation of an intrachain cyclized disulfide and leads to the appearance of half-antibodies, which contain non-covalently linked heavy chains as determined by analysis of IgG4 antibodies under denaturing conditions (51, 52). Thus, IgG4 antibodies can exchange Fab arms by swapping a heavy chain and attached light chain and form bispecific antibodies that function as monovalent molecules (Fig. 3) (51, 53).

Bottom Line: IgG4-related disease (IgG4-RD) is a novel clinical entity proposed in Japan in the 21th century and is attracting strong attention over the world.The characteristic manifestations of IgG4-RD are increased serum IgG4 concentration and tumefaction by IgG4(+) plasma cells.Recently, many reports of aberrant acquired immunity such as Th2-diminated immune responses have been published.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan Department of Clinical Immunology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan Present address: Department of Clinical Immunology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan umehara606@gmail.com.

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Related in: MedlinePlus