title: Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.
abstract: Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN), at least in part, are localized in bone marrow (BM). Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT) from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly) independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN) contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6). Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC) as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aizawa
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Huihua
authors.initials: H
authors.lastname: Pang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kihara
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Nakata
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamaji
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000378:metabolism; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G
references.citation: Kidney Int. 1986 Feb;29(2):557-62
references.pmid: 3702213
references.citation: J Clin Pathol. 1993 Jul;46(7):607-10
references.pmid: 8157744
references.citation: Arthritis Rheum. 2007 Jul;56(7):2362-70
references.pmid: 17599764
references.citation: Nat Genet. 2000 Nov;26(3):354-7
references.pmid: 11062479
references.citation: J Immunol. 2002 Oct 15;169(8):4136-46
references.pmid: 12370342
references.citation: Q J Med. 1984 Spring;53(210):227-50
references.pmid: 6463197
references.citation: Am J Hum Genet. 2002 Mar;70(3):781-6
references.pmid: 11828340
references.citation: Clin Nephrol. 1979 Jan;11(1):39-44
references.pmid: 428155
references.citation: Clin Dev Immunol. 2011;2011:819646
references.pmid: 21765852
references.citation: Kidney Int. 2001 Sep;60(3):969-73
references.pmid: 11532091
references.citation: Am J Physiol Renal Physiol. 2007 Jan;292(1):F330-9
references.pmid: 16804106
references.citation: Am J Pathol. 2007 Feb;170(2):447-56
references.pmid: 17255313
references.citation: Nat Genet. 1999 May;22(1):74-7
references.pmid: 10319865
references.citation: Kidney Int. 1990 Dec;38(6):1216-29
references.pmid: 2074665
references.citation: Clin J Am Soc Nephrol. 2008 Sep;3(5):1301-7
references.pmid: 18508946
references.citation: Food Chem Toxicol. 1989 Jun;27(6):361-8
references.pmid: 2676788
references.citation: J Am Soc Nephrol. 2011 Oct;22(10):1795-803
references.pmid: 21949093
references.citation: Nephron Exp Nephrol. 2003;95(1):e36-42
references.pmid: 14520013
references.citation: J Clin Lab Anal. 1998;12(1):1-5
references.pmid: 9484662
references.citation: J Clin Invest. 1999 Jul;104(1):73-81
references.pmid: 10393701
references.citation: JAMA. 1978 May 12;239(19):2019-20
references.pmid: 147951
references.citation: J Clin Invest. 2009 Jun;119(6):1668-77
references.pmid: 19478457
references.citation: Kidney Int. 2004 Apr;65(4):1135-44
references.pmid: 15086452
references.citation: Lab Invest. 1989 Apr;60(4):499-506
references.pmid: 2709812
references.citation: Contrib Nephrol. 2007;157:164-8
references.pmid: 17495457
references.citation: J Am Soc Nephrol. 2009 Dec;20(12):2518-24
references.pmid: 19820122
references.citation: Inflamm Res. 2003 Oct;52(10):428-32
references.pmid: 14520519
references.citation: Kidney Int. 1996 Sep;50(3):952-61
references.pmid: 8872971
references.citation: Lab Invest. 1992 Sep;67(3):379-86
references.pmid: 1328763
references.citation: J Urol Nephrol (Paris). 1968 Sep;74(9):694-5
references.pmid: 4180586
references.citation: Am J Pathol. 2012 Oct;181(4):1338-47
references.pmid: 22871574
references.citation: J Am Soc Nephrol. 2005 Jul;16(7):2088-97
references.pmid: 15930092
references.citation: Kidney Int. 2002 Dec;62(6):2022-34
references.pmid: 12427126
references.citation: Virchows Arch A Pathol Anat Histol. 1981;392(1):45-54
references.pmid: 7281501
references.citation: J Am Soc Nephrol. 2008 Dec;19(12):2384-95
references.pmid: 18776126
references.citation: Kidney Int. 1993 Nov;44(5):1036-47
references.pmid: 8264133
references.citation: J Am Soc Nephrol. 2008 May;19(5):1008-14
references.pmid: 18272841
references.citation: Kidney Int. 1986 Dec;30(6):924-31
references.pmid: 3493382
references.citation: Nephrol Dial Transplant. 2003 Dec;18(12):2505-14
references.pmid: 14605272
references.citation: J Am Soc Nephrol. 2005 May;16(5):1289-99
references.pmid: 15772254
references.citation: Am J Pathol. 2002 Oct;161(4):1497-505
references.pmid: 12368222
references.citation: Clin Nephrol. 1984 Jan;21(1):7-14
references.pmid: 6231147
references.citation: J Immunol. 2003 Mar 15;170(6):3243-53
references.pmid: 12626583
references.citation: Kidney Int. 1985 May;27(5):756-61
references.pmid: 4021309
references.citation: Kidney Int. 2008 Jun;73(12):1426-33
references.pmid: 18354379
references.citation: Nephron. 1992;62(3):328-31
references.pmid: 1436347
references.citation: J Am Soc Nephrol. 2012 Aug;23(8):1364-74
references.pmid: 22797187
references.citation: Am J Kidney Dis. 1988 Nov;12(5):410-4
references.pmid: 3189325
references.citation: Kidney Int. 1998 Oct;54(4):1166-74
references.pmid: 9767532
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2482-6
references.pmid: 15695334
references.citation: Nephrol Dial Transplant. 2012 Mar;27(3):1090-7
references.pmid: 21778277
references.citation: N Engl J Med. 1981 Nov 5;305(19):1159-60
references.pmid: 7290130
references.citation: J Clin Pathol. 1996 Jan;49(1):38-42
references.pmid: 8666683
references.citation: Kidney Int. 2001 Mar;59(3):1077-85
references.pmid: 11231363
references.citation: Clin Nephrol. 1998 Jan;49(1):1-8
references.pmid: 9491278
references.citation: Kidney Int. 2007 Aug;72(3):319-27
references.pmid: 17495863
references.citation: Springer Semin Immunopathol. 1982;5(3):321-32
references.pmid: 6223392
references.citation: Nephrol Dial Transplant. 2013 Feb;28(2):320-6
references.pmid: 23136213
references.citation: Nephron Clin Pract. 2003;93(4):c137-45
references.pmid: 12759582
references.citation: J Clin Invest. 1989 Oct;84(4):1070-5
references.pmid: 2794045
references.citation: J Clin Invest. 2009 Jun;119(6):1450-2
references.pmid: 19504718
references.citation: Contrib Nephrol. 2007;157:70-9
references.pmid: 17495440
references.citation: Intern Med. 2006;45(22):1291-5
references.pmid: 17170503