IgA nephropathy: molecular mechanisms of the disease.

@article{Mestecky2013IgANM,
  title={IgA nephropathy: molecular mechanisms of the disease.},
  author={Jiri F. Mestecky and Milan Ra{\vs}ka and Bruce A Julian and Ali G. Gharavi and Matthew B. Renfrow and Zina Moldoveanu and Lea Novak and Karel Matou{\vs}ovic and Jan Novak},
  journal={Annual review of pathology},
  year={2013},
  volume={8},
  pages={
          217-40
        }
}
Studies of molecular and cellular interactions involved in the pathogenesis of IgA nephropathy have revealed the autoimmune nature of this most common primary glomerulonephritis. In patients with this disease, altered glycan structures in the unique hinge region of the heavy chains of IgA1 molecules lead to the exposure of antigenic determinants, which are recognized by naturally occurring antiglycan antibodies of the IgG and/or IgA1 isotype. As a result, nephritogenic immune complexes form in… 

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References

SHOWING 1-10 OF 150 REFERENCES

Progress in Molecular and Genetic Studies of IgA Nephropathy

Recent progress in molecular analyses of IgA nephropathy defines this disease as an autoimmune process with a novel IgA mesangial receptor and certain genetically determined traits.

The pathophysiology of IgA nephropathy.

Recent advances in understanding the biochemical, immunologic, and genetic pathogenesis of IgA nephropathy are discussed, and five distinct susceptibility loci are identified that potentially influence these processes and contain candidate mediators of disease.

The pathogenesis of IgA nephropathy

  • R. Glassock
  • Biology, Medicine
    Current opinion in nephrology and hypertension
  • 2011
Progress in understanding the details of the pathogenesis of IgA nephropathy will lead to a better means of diagnosis, more accurate individualized prognosis and personalized treatment regimens for this globally distributed and very common primary glomerular disease.

The genetics of IgA nephropathy

The evidence for genetic contributions to the disease, clinical patterns of familial disease, and some of the most promising genetic studies conducted to date are presented.

Aberrant glycosylation of IgA1 and anti-glycan antibodies in IgA nephropathy: role of mucosal immune system.

IgA nephropathy is an auto-immune disease, induced by mesangial deposition of circulating complexes containing galactose-deficient IgA1, and the aberrant glycosylation of IgA 1 may reflect abnormal mucosal immune responses to infections of the upper respiratory tract in genetically predisposed individuals.

AUTOIMMUNITY IN IgA NEPHROPATHY

Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus.

To further characterize the IgA deposits found in glomeruli of patients with IgA nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus, renal biopsies from patients with

Recent advances in IgA nephropathy--the glomerulopodocytic-tubular communication.

In vitro study implicates humoral factors released from mesangial cells alter the glomerular permeability in the event of proteinuria and tubulointerstitial injury in IgAN, leading to subsequent inflammatory changes in the renal tubulointerstitium.

The glomerular response to IgA deposition in IgA nephropathy.

IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells.

It is suggested that CIC containing aberrantly glycosylated IgA1 affect proliferation of MC in vitro and, thus, likely play a role in the pathogenesis of IgAN.
...