Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment.
J Clin Med
; 10(19)2021 Sep 29.
Article
en En
| MEDLINE
| ID: mdl-34640530
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
J Clin Med
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos