Next Article in Journal
Postoperative Pain following Root Canal Filling with Bioceramic vs. Traditional Filling Techniques: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Next Article in Special Issue
The Contribution of Complement to the Pathogenesis of IgA Nephropathy: Are Complement-Targeted Therapies Moving from Rare Disorders to More Common Diseases?
Previous Article in Journal
Predictors of Effectiveness of Platelet-Rich Plasma Therapy for Knee Osteoarthritis: A Retrospective Cohort Study
Previous Article in Special Issue
The Role of Complement Component C3 Activation in the Clinical Presentation and Prognosis of IgA Nephropathy—A National Study in Children
 
 
Review

Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

1
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Juan F. Navarro-González
J. Clin. Med. 2021, 10(19), 4501; https://doi.org/10.3390/jcm10194501
Received: 30 August 2021 / Accepted: 22 September 2021 / Published: 29 September 2021
(This article belongs to the Special Issue New Insights into the Pathogenesis and Therapies of IgA Nephropathy)
IgA nephropathy, initially described in 1968 as a kidney disease with glomerular “intercapillary deposits of IgA-IgG”, has no disease-specific treatment and is a common cause of kidney failure. Clinical observations and laboratory analyses suggest that IgA nephropathy is an autoimmune disease wherein the kidneys are damaged as innocent bystanders due to deposition of IgA1-IgG immune complexes from the circulation. A multi-hit hypothesis for the pathogenesis of IgA nephropathy describes four sequential steps in disease development. Specifically, patients with IgA nephropathy have elevated circulating levels of IgA1 with some O-glycans deficient in galactose (galactose-deficient IgA1) and these IgA1 glycoforms are recognized as autoantigens by unique IgG autoantibodies, resulting in formation of circulating immune complexes, some of which deposit in glomeruli and activate mesangial cells to induce kidney injury. This proposed mechanism is supported by observations that (i) glomerular immunodeposits in patients with IgA nephropathy are enriched for galactose-deficient IgA1 glycoforms and the corresponding IgG autoantibodies; (ii) circulatory levels of galactose-deficient IgA1 and IgG autoantibodies predict disease progression; and (iii) pathogenic potential of galactose-deficient IgA1 and IgG autoantibodies was demonstrated in vivo. Thus, a better understanding of the structure–function of these immunoglobulins as autoantibodies and autoantigens will enable development of disease-specific treatments. View Full-Text
Keywords: IgA nephropathy; O-glycosylation; IgA1; autoantibody; immune complex IgA nephropathy; O-glycosylation; IgA1; autoantibody; immune complex
Show Figures

Figure 1

MDPI and ACS Style

Knoppova, B.; Reily, C.; King, R.G.; Julian, B.A.; Novak, J.; Green, T.J. Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment. J. Clin. Med. 2021, 10, 4501. https://doi.org/10.3390/jcm10194501

AMA Style

Knoppova B, Reily C, King RG, Julian BA, Novak J, Green TJ. Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment. Journal of Clinical Medicine. 2021; 10(19):4501. https://doi.org/10.3390/jcm10194501

Chicago/Turabian Style

Knoppova, Barbora, Colin Reily, R. Glenn King, Bruce A. Julian, Jan Novak, and Todd J. Green. 2021. "Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment" Journal of Clinical Medicine 10, no. 19: 4501. https://doi.org/10.3390/jcm10194501

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop