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Identification of IgA autoantibodies targeting mesangial cells redefines the pathogenesis of IgA nephropathy. 2023

Yoshihito Nihei, and Kei Haniuda, and Mizuki Higashiyama, and Shohei Asami, and Hiroyuki Iwasaki, and Yusuke Fukao, and Maiko Nakayama, and Hitoshi Suzuki, and Mika Kikkawa, and Saiko Kazuno, and Yoshiki Miura, and Yusuke Suzuki, and Daisuke Kitamura
Department of Nephrology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common type of primary glomerulonephritis, often progressing to renal failure. IgAN is triggered by IgA deposition in the glomerular mesangium by an undefined mechanism. Here, we show that grouped ddY (gddY) mice, a spontaneous IgAN model, produce serum IgA against mesangial antigens, including βII-spectrin. Most patients with IgAN also have serum anti-βII-spectrin IgA. As in patients with IgAN, IgA+ plasmablasts accumulate in the kidneys of gddY mice. IgA antibodies cloned from the plasmablasts carry substantial V-region mutations and bind to βII-spectrin and the surface of mesangial cells. These IgAs recognize transfected and endogenous βII-spectrin exposed on the surface of embryonic kidney-derived cells. Last, we demonstrate that the cloned IgA can bind selectively to glomerular mesangial regions in situ. The identification of IgA autoantibody and its antigen in IgAN provides key insights into disease onset and redefines IgAN as a tissue-specific autoimmune disease.

UI MeSH Term Description Entries
D007070 Immunoglobulin A Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions. IgA,IgA Antibody,IgA1,IgA2,Antibody, IgA
D005922 Glomerulonephritis, IGA A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE. Berger Disease,Immunoglobulin A Nephropathy,Nephropathy, IGA,Berger's Disease,IGA Glomerulonephritis,IGA Nephropathy,Iga Nephropathy 1,Nephritis, IGA Type,Bergers Disease,Glomerulonephritides, IGA,IGA Type Nephritis,Nephropathy 1, Iga,Nephropathy, Immunoglobulin A
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D013049 Spectrin A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. alpha-Spectrin,beta-Spectrin,alpha Spectrin,beta Spectrin
D050527 Mesangial Cells Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM. Glomerular Mesangial Cells,Extraglomerular Mesangial Cells,Lacis Cells,Mesangial Cells, Kidney,Renal Glomerulus Mesangial Cells,Renal Mesangial Cells,Cell, Extraglomerular Mesangial,Cell, Glomerular Mesangial,Cell, Kidney Mesangial,Cell, Lacis,Cell, Mesangial,Cell, Renal Mesangial,Cells, Extraglomerular Mesangial,Cells, Glomerular Mesangial,Cells, Kidney Mesangial,Cells, Lacis,Cells, Mesangial,Cells, Renal Mesangial,Extraglomerular Mesangial Cell,Glomerular Mesangial Cell,Kidney Mesangial Cell,Kidney Mesangial Cells,Lacis Cell,Mesangial Cell,Mesangial Cell, Extraglomerular,Mesangial Cell, Glomerular,Mesangial Cell, Kidney,Mesangial Cell, Renal,Mesangial Cells, Extraglomerular,Mesangial Cells, Glomerular,Mesangial Cells, Renal,Renal Mesangial Cell
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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