Role of macromolecular IgA in IgA nephropathy

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Presentation transcript:

Role of macromolecular IgA in IgA nephropathy Paul J.M. Van Der Boog, Cees Van Kooten, Johan W. De Fijter, Mohamed R. Daha Kidney International Volume 67, Issue 3, Pages 813-821 (March 2005) DOI: 10.1111/j.1523-1755.2005.00146.x Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 1 Schematic representation of different forms of immunoglobulin A (IgA) in the circulation. Serum IgA consists of monomeric IgA (mIgA),dimeric IgA (dIgA), which includes two mIgA joined by J chain) and polymeric IgA (pIgA). Although mIgA and IgA have a well-defined molecular composition, pIgA may be present as mIgA and/or dIgA containing aggregates or immune complexes or IgA associated with other proteins. Kidney International 2005 67, 813-821DOI: (10.1111/j.1523-1755.2005.00146.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 2 Structure of immunoglobulin A (IgA1) and the amino acid sequence in the hinge region and possible O-glycan structures. Each IgA1 hinge region possesses nine O-linked oligosaccharide (O-glycan) side chains (five serine and four threonine). The hydroxy group of serine or threonine is linked to the α-anomeric carbon atom in N-acetylgalactosamine (GalNAc). The GalNAc residue may be extended with β1,3-linked galactose (Gal). Further, N-acetylneuraminic acid (NANA) (sialic acid) could bind to Gal through an α2,3 link and to GalNAc through an α2,6 link. Kidney International 2005 67, 813-821DOI: (10.1111/j.1523-1755.2005.00146.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 3 Molecular composition of serum immunoglobulin A (IgA). Size fractionation of human serum shows the presence of monomeric IgA (mIgA), dimeric IgA (dIgA) and polymeric IgA (pIgA). High-molecular-weight IgA (HMW-IgA) or macromolecular IgA has been defined as the dimeric and polymeric IgA fractions together (upper part of figure). Aggregates of IgA, IgA-containing immune complexes, or complexes of IgA associated with other proteins may be present in both dimeric and polymeric fractions (lower part of figure). Kidney International 2005 67, 813-821DOI: (10.1111/j.1523-1755.2005.00146.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 4 The three pathways of complement activation. Each complement-activation pathway generates a C3 convertase (C4b2a/C3bBbP), which mediates cleavage of C3, followed by activation of the terminal complement pathway and formation of the membane attack complex. Kidney International 2005 67, 813-821DOI: (10.1111/j.1523-1755.2005.00146.x) Copyright © 2005 International Society of Nephrology Terms and Conditions