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IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition.

In English

Författare

  • Zeliha Oruc
  • Christelle Oblet
  • Ahmed Boumediene
  • Anne Druilhe
  • Virginie Pascal
  • Elisabeth Le Rumeur
  • Armelle Cuvillier
  • Chahrazed El Hamel
  • Sandrine Lecardeur
  • Tomas Leanderson
  • Willy Morelle
  • Jocelyne Demengeot
  • Jean-Claude Aldigier
  • Michel Cogné
Visa allt

Summary, in English

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.

Avdelning/ar

  • Immunology

Publiceringsår

2016-09

Språk

Engelska

Sidor

2748-2761

Publikation/Tidskrift/Serie

Journal of the American Society of Nephrology: JASN

Volym

27

Issue

9

Dokumenttyp

Artikel i tidskrift

Förlag

American Society of Nephrology

Ämne

  • Urology and Nephrology

Status

Published

Forskningsgrupp

  • Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1533-3450