IgA vasculitis with nephritis: update of pathogenesis with clinical implications.
Pediatr Nephrol
; 37(4): 719-733, 2022 04.
Article
en En
| MEDLINE
| ID: mdl-33818625
ABSTRACT
IgA vasculitis with nephritis (IgAVN) shares many pathogenetic features with IgA nephropathy (IgAN). The purpose of this review is to describe our current understanding of the pathogenesis of pediatric IgAVN, particularly as it relates to the four-hit hypothesis for IgAN. These individual steps, i.e., hits, in the pathogenesis of IgAN are (1) elevated production of IgA1 glycoforms with some O-glycans deficient in galactose (galactose-deficient IgA1; Gd-IgA1), (2) generation of circulating IgG autoantibodies specific for Gd-IgA1, (3) formation of pathogenic circulating Gd-IgA1-containing immune complexes, and (4) kidney deposition of the Gd-IgA1-IgG immune complexes from the circulation and induction of glomerular injury. Evidence supporting the four-hit hypothesis in the pathogenesis of pediatric IgAVN is detailed. The genetics, pediatric outcomes, and kidney histopathologic features and the impact of these findings on future treatment and potential biomarkers are discussed. In summary, the evidence points to the critical roles of Gd-IgA1-IgG immune complexes and complement activation in the pathogenesis of IgAVN. Future studies are needed to characterize the features of the immune and autoimmune responses that enable progression of IgA vasculitis to IgAVN.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vasculitis por IgA
/
Glomerulonefritis por IGA
/
Nefritis
Tipo de estudio:
Etiology_studies
Límite:
Child
/
Humans
Idioma:
En
Revista:
Pediatr Nephrol
Asunto de la revista:
NEFROLOGIA
/
PEDIATRIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos