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Review
. 2022 Feb;49(1):8-21.
doi: 10.1111/iji.12561. Epub 2021 Nov 24.

Immunological drivers of IgA nephropathy: Exploring the mucosa-kidney link

Haresh Selvaskandan  1 , Jonathan Barratt  1 , Chee Kay Cheung  1
Affiliations
Review

Immunological drivers of IgA nephropathy: Exploring the mucosa-kidney link

Haresh Selvaskandan et al. Int J Immunogenet. 2022 Feb.

Abstract

IgA nephropathy (IgAN) is the most common pattern of primary glomerular disease reported worldwide. Up to 40% of those with IgAN progress to end-stage kidney disease within 20 years of diagnosis, with no currently available disease-specific treatment. This is likely to change rapidly, with evolving insights into the mechanisms driving this disease. IgAN is an immune-complex-mediated disease, and its pathophysiology has been framed by the 'four-hit hypothesis', which necessitates four events to occur for clinically significant disease to develop. However, this hypothesis does not explain the wide variability observed in its presentation or clinical progression. Recently, there has been great interest in exploring the role of the mucosal immune system in IgAN, especially given the well-established link between mucosal infections and disease flares. Knowledge of antigen-mucosal interactions is now being successfully leveraged for therapeutic purposes; the gut-directed drug Nefecon (targeted release formulation-budesonide) is on track to become the first medication to be approved specifically for the treatment of IgAN. In this review, we examine established immunological paradigms in IgAN, explore how antigen-mucosal immune responses drive disease, and discuss how this knowledge is being used to develop new treatments.

Keywords: IgA nephropathy; immunology; mucosa; mucosa-kidney axis; treatment.

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References

REFERENCES

    1. Allen, A. C., Bailey, E. M., Barratt, J., Buck, K. S., & Feehally, J. (1999). Analysis of IgA1 O-glycans in IgA nephropathy by fluorophore-assisted carbohydrate electrophoresis. Journal of the American Society of Nephrology, 10(8), 1763-1771.
    1. Allen, A. C., Bailey, E. M., Brenchley, P. E., Buck, K. S., Barratt, J., & Feehally, J. (2001). Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: Observations in three patients. Kidney International, 60(3), 969-973. https://doi.org/10.1046/j.1523-1755.2001.060003969.x
    1. Allen, A. C., Harper, S. J., & Feehally, J. (1995). Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy. Clinical and Experimental Immunology, 100(3), 470-474.
    1. Barbour, S. J., Coppo, R., Zhang, H., Liu, Z., Suzuki, Y., Matsuzaki, K., Katafuchi, R., Er, L., Espino-Hernandez, G., Kim, S. J., Reich, H. N., Feehally, J., & Cattran, D. C. (2019). Evaluating a new international risk-prediction tool in IgA nephropathy. JAMA Internal Medicine, 179(7), 942-952. https://doi.org/10.1001/jamainternmed.2019.0600
    1. Barratt, J., Bailey, E. M., Buck, K. S., Mailley, J., Moayyedi, P., Feehally, J., Turney, J. H., Crabtree, J. E., & Allen, A. C. (1999). Exaggerated systemic antibody response to mucosal helicobacter pylori infection in IgA nephropathy. American Journal of Kidney Diseases, 33(6), 1049-1057. https://doi.org/10.1016/S0272-6386(99)70141-1

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