Document details

IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition

Author(s): Oruc, Zeliha ; Oblet, Christelle ; Boumediene, Ahmed ; Druilhe, Anne ; Pascal, Virginie ; Le Rumeur, Elisabeth ; Cuvillier, Armelle ; El Hamel, Chahrazed ; Lecardeur, Sandrine ; Leanderson, Tomas ; Morelle, Willy ; Demengeot, Jocelyne ; Aldigier, Jean-Claude ; Cogné, Michel

Date: 2016

Persistent ID: http://hdl.handle.net/10400.7/846

Origin: ARCA - Access to Research and Communication Annals

Subject(s): IgA nephropathy; IgA deposition; IgA; transgenic mouse; Immunology and pathology


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This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004660/

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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.

Agence Nationale de la Recherche; Ligue Nationale contre le Cancer; Conseil Régional du Limousin; European Community grants: (Fonds Européens de Développement Régional); Région Nord-Pas de Calais (France); Université des Sciences et Technologies de Lille 1.

Document Type Journal article
Language English
Contributor(s) ARCA
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