IgA Hinge Glycosylation in IgA Nephropathy and IgA Vasculitis

Nikolay Bulanov
Sechenov First Moscow State Medical University, Russia

Immunoglobulin A (IgA) deposits in the glomeruli – the hallmark feature of IgA nephropathy – were first described in 1968 by Jean Berger and Nicole Hinglais (1). However, the underlying mechanisms of mesangial IgA deposition in the glomeruli couldn't be explained until the mid-90s. In 1995, Alice C. Allen et al. studied serum IgA1, IgG, and C1 inhibitor glycosylation in several patients with biopsy-proven IgA nephropathy (IgAN) and healthy controls. IgAl from patients with IgAN showed significantly higher binding than controls to lectins specific for O-linked N-acetyl galactosamine that indicated reduced terminal galactosylation of the hinge region O-linked moieties (2). In 1998, Allen et al. found a similar increase in IgA1 lectin binding in both adults and children with Henoch-Schönlein purpura (currently known as IgA vasculitis) with kidney involvement compared to other forms of glomerulonephritis and controls (3). In 1999, Milan Tomana et al. showed that circulating immune complexes (CICs) isolated from sera of patients with IgAN consisted of undergalactosylated polymeric IgA1 and IgG antibodies specific for N-acetyl galactosamine residues in O-linked glycans of the hinge region of IgA1 heavy chains (4). These studies provided insights into immunological abnormalities resulting in the formation of CICs containing aberrantly glycosylated IgA1 that escape removal through the reticuloendothelial system and form mesangial deposits in IgAN and IgA vasculitis.

References

  1. Berger J, Hinglais N. Les depots intercapillaires d'IgA-IgG. J Urol Nephrol. 1968; 74:694–95.
  2. Allen AC, Harper SJ, Feehally J. Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clin Exp Immunol. 1995; 100:470–474.
  3. Allen AC, Willis FR, Beattie TJ, Feehally J. Abnormal IgA glycosylation in Henoch-Schönlein purpura restricted to patients with clinical nephritis. Nephrol Dialysis Transplant. 1998; 13:930–934.
  4. Tomana M, Novak J, Julian BA, et al. Circulating immune complexes in IgA nephropathy consist of IgA with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest. 1999; 104:73–81.

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