Titre :

IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition

Auteur(s) :

Oruc, Zeliha [Auteur]
Oblet, Christelle [Auteur]
Boumediene, Ahmed [Auteur]
Druilhe, Anne [Auteur]
Pascal, Virginie [Auteur]
Le Rumeur, Elisabeth [Auteur]
Cuvillier, Armelle [Auteur]
El Hamel, Chahrazed [Auteur]
Lecardeur, Sandrine [Auteur]
Leanderson, Tomas [Auteur]
Morelle, Willy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Demengeot, Jocelyne [Auteur]
Aldigier, Jean-Claude [Auteur]
Cogné, Michel [Auteur]

Titre de la revue :

Journal of the American Society of Nephrology. JASN

Nom court de la revue :

J. Am. Soc. Nephrol.

Numéro :

27

Pagination :

2748-2761

Date de publication :

2016-09

ISSN :

1533-3450

Mot(s)-clé(s) en anglais :

IgA
Immunology and pathology
Male
Glomerular Mesangium
Immunoglobulin A
IgA deposition
transgenic mouse
Animals
IgA nephropathy
Antibody Formation
Female
Protein Conformation
Mice

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch-Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, ...
Lire la suite >IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch-Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen-free environment had less IgA deposition. However, serum IgA of specific pathogen-free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α1KI, and even J chain-deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post-translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.Lire moins >

Langue :

Anglais

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Mécanismes moléculaires de la N-glycosylation et pathologies associées

Date de dépôt :

2020-02-12T15:12:00Z