title: IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition.
abstract: 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.
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Oruc
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Christelle
authors.initials: C
authors.lastname: Oblet
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Ahmed
authors.initials: A
authors.lastname: Boumediene
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Druilhe
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Virginie
authors.initials: V
authors.lastname: Pascal
authors.affiliation: Genetics and Development Instittute, Rennes University, Centre National de la Recherche Scientifique, Rennes, France;
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Le Rumeur
authors.affiliation: B Cell Design, Limoges, France;
authors.forename: Armelle
authors.initials: A
authors.lastname: Cuvillier
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Chahrazed
authors.initials: C
authors.lastname: El Hamel
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lecardeur
authors.affiliation: Immunology Group, Lund University, Lund, Sweden;
authors.forename: Tomas
authors.initials: T
authors.lastname: Leanderson
authors.affiliation: Centre National de la Recherche Scientifique, Laboratory of Structural and Functional Glycobiology, University of Lille 1, France; and.
authors.forename: Willy
authors.initials: W
authors.lastname: Morelle
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Demengeot
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France;
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Aldigier
authors.affiliation: Limoges University Hospital Dupuytren, Centre National de la Recherche Scientifique, Limoges University, Limoges, France; cogne@unilim.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
mesh_terms: D000818:Animals; D000917:Antibody Formation; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism*; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D011487:Protein Conformation
chemical_list: D007070:Immunoglobulin A
keywords: IgA; IgA deposition; IgA nephropathy; Immunology and pathology; transgenic mouse
references.citation: Methods Mol Biol. 2009;534:5-21
references.pmid: 19277556
references.citation: Kidney Int. 2001 Jan;59(1):277-85
references.pmid: 11135081
references.citation: Kidney Int. 2010 Feb;77(3):181-6
references.pmid: 19924103
references.citation: Kidney Int. 1985 May;27(5):756-61
references.pmid: 4021309
references.citation: Blood. 2015 Aug 6;126(6):757-65
references.pmid: 26113545
references.citation: J Am Soc Nephrol. 2008 May;19(5):1008-14
references.pmid: 18272841
references.citation: J Biol Chem. 2009 Mar 27;284(13):8822-32
references.pmid: 19158079
references.citation: J Am Soc Nephrol. 1992 Apr;2(10 Suppl):S173-80
references.pmid: 1600133
references.citation: Semin Immunopathol. 2012 May;34(3):365-82
references.pmid: 22434325
references.citation: Nephrol Dial Transplant. 2011 Dec;26(12):3930-7
references.pmid: 21459784
references.citation: Cell. 2010 Mar 19;140(6):859-70
references.pmid: 20303876
references.citation: Clin Exp Immunol. 1995 Jun;100(3):470-4
references.pmid: 7774058
references.citation: Clin J Am Soc Nephrol. 2011 Sep;6(9):2165-74
references.pmid: 21784830
references.citation: Eur J Immunol. 1998 Aug;28(8):2355-65
references.pmid: 9710213
references.citation: Kidney Int. 2004 Jul;66(1):121-32
references.pmid: 15200419
references.citation: Nephron. 1994;66(1):38-44
references.pmid: 8107951
references.citation: Nat Protoc. 2007;2(7):1585-602
references.pmid: 17585300
references.citation: Kidney Int. 2001 Mar;59(3):1077-85
references.pmid: 11231363
references.citation: Methods Mol Biol. 2002;193:301-27
references.pmid: 12325520
references.citation: Gut. 1992 Apr;33(4):476-8
references.pmid: 1582590
references.citation: J Immunol. 2002 Aug 1;169(3):1357-64
references.pmid: 12133959
references.citation: J Am Soc Nephrol. 2012 Mar;23(3):371-3
references.pmid: 22323642
references.citation: J Clin Invest. 1991 Nov;88(5):1522-30
references.pmid: 1939642
references.citation: J Exp Med. 2000 Jun 5;191(11):1999-2009
references.pmid: 10839814
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3064-9
references.pmid: 20133609
references.citation: J Clin Invest. 2009 Sep;119(9):2441-50
references.pmid: 19729841
references.citation: J Clin Invest. 2009 Jun;119(6):1668-77
references.pmid: 19478457
references.citation: J Immunol. 1993 Apr 15;150(8 Pt 1):3561-8
references.pmid: 8468490
references.citation: J Clin Pathol. 1993 Jul;46(7):607-10
references.pmid: 8157744
references.citation: Kidney Int. 2007 Jun;71(11):1148-54
references.pmid: 17342176
references.citation: Glycobiology. 2006 May;16(5):440-61
references.pmid: 16449350
references.citation: Kidney Int. 2001 Sep;60(3):969-73
references.pmid: 11532091
references.citation: Contrib Nephrol. 1993;104:162-71
references.pmid: 8325027
references.citation: Kidney Int. 2003 Jun;63(6):2286-94
references.pmid: 12753320
references.citation: J Immunol Methods. 2004 Nov;294(1-2):199-207
references.pmid: 15604028
references.citation: J Am Soc Nephrol. 2012 Mar;23(3):438-46
references.pmid: 22193386
references.citation: Nat Rev Immunol. 2010 Mar;10(3):159-69
references.pmid: 20182457
references.citation: J Exp Med. 2012 Apr 9;209(4):793-806
references.pmid: 22451718
references.citation: Clin Exp Immunol. 1988 Aug;73(2):300-6
references.pmid: 3052947
references.citation: Kidney Int. 1997 Aug;52(2):509-16
references.pmid: 9264010
references.citation: Scand J Urol Nephrol. 1997 Jun;31(3):289-93
references.pmid: 9249895
references.citation: J Mol Biol. 2004 Nov 19;344(2):495-511
references.pmid: 15522301
references.citation: Kidney Int. 2005 Feb;67(2):504-13
references.pmid: 15673298
references.citation: Immunity. 2009 Oct 16;31(4):677-89
references.pmid: 19833089
references.citation: Am J Kidney Dis. 2000 Sep;36(3):E19
references.pmid: 10977812
references.citation: J Clin Invest. 1999 Jul;104(1):73-81
references.pmid: 10393701
references.citation: N Engl J Med. 2002 Sep 5;347(10):738-48
references.pmid: 12213946