Patients with Proliferative Lupus Nephritis Have Autoantibodies That React to Moesin and Demonstrate Increased Glomerular Moesin Expression.

autoantibodies glomerulonephritis lupus nephritis systemic lupus erythematosus target antigens

Journal

Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588

Informations de publication

Date de publication:
16 Feb 2021
Historique:
received: 04 01 2021
revised: 28 01 2021
accepted: 08 02 2021
entrez: 6 3 2021
pubmed: 7 3 2021
medline: 7 3 2021
Statut: epublish

Résumé

Kidney involvement in systemic lupus erythematosus (SLE)-termed lupus nephritis (LN)-is a severe manifestation of SLE that can lead to end-stage kidney disease (ESKD). LN is characterized by immune complex deposition and inflammation in the glomerulus. We tested the hypothesis that autoantibodies targeting podocyte and glomerular cell proteins contribute to the development of immune complex formation in LN. We used Western blotting with SLE sera from patients with and without LN to identify target antigens in human glomerular and cultured human-derived podocyte membrane proteins. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified the proteins in the gel regions corresponding to reactive bands observed with sera from LN patients. We identified 102 proteins that were present in both the podocyte and glomerular samples. We identified 10 high-probability candidates, including moesin, using bioinformatic analysis. Confirmation of moesin as a target antigen was conducted using immunohistochemical analysis (IHC) of kidney biopsy tissue and enzyme-linked immunosorbent assay (ELISA) to detect circulating antibodies. By IHC, biopsies from patients with proliferative lupus nephritis (PLN, class III/IV) demonstrated significantly increased glomerular expression of moesin (

Identifiants

pubmed: 33669337
pii: jcm10040793
doi: 10.3390/jcm10040793
pmc: PMC7920286
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NIH HHS
ID : R01AI024717
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI130830
Pays : United States
Organisme : NIH HHS
ID : K08DK102542
Pays : United States
Organisme : U.S. Department of Veterans Affairs
ID : I01BX001834
Organisme : NIH HHS
ID : U01AI130830
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK102542
Pays : United States

Références

Nephrol Dial Transplant. 2014 Jun;29(6):1168-77
pubmed: 24319012
Lupus. 2017 Jul;26(8):815-824
pubmed: 28420046
J Am Soc Nephrol. 2002 Mar;13(3):630-8
pubmed: 11856766
Kidney Int. 2012 Jul;82(2):184-92
pubmed: 22297676
Genes Immun. 2012 Apr;13(3):232-8
pubmed: 22189356
Clin Rev Allergy Immunol. 2011 Jun;40(3):151-8
pubmed: 20414746
Clin J Am Soc Nephrol. 2013 Oct;8(10):1702-8
pubmed: 23833315
Kidney Int. 2010 Nov;78(9):868-82
pubmed: 20664558
Clin Dev Immunol. 2012;2012:579670
pubmed: 22162716
J Mol Med (Berl). 2008 Dec;86(12):1379-94
pubmed: 18773185
N Engl J Med. 2014 Dec 11;371(24):2277-2287
pubmed: 25394321
J Immunol. 2009 Jan 1;182(1):703-10
pubmed: 19109204
N Engl J Med. 2009 Jul 2;361(1):11-21
pubmed: 19571279
Protein Pept Lett. 2018;25(4):350-355
pubmed: 29557737
Clin Exp Nephrol. 2013 Oct;17(5):638-641
pubmed: 24072414
Thromb Res. 2015 May;135(5):867-72
pubmed: 25743886
N Engl J Med. 2011 Dec 1;365(22):2110-21
pubmed: 22129255
J Clin Pathol. 2006 Sep;59(9):916-20
pubmed: 16522749
Autoimmune Dis. 2014;2014:321359
pubmed: 24649358
Cell Stress Chaperones. 2016 Jan;21(1):155-166
pubmed: 26483256
Mamm Genome. 2008 Jan;19(1):41-50
pubmed: 18064521
J Proteomics. 2011 Sep 6;74(10):2008-17
pubmed: 21640210
Arthritis Res Ther. 2017 Jun 6;19(1):125
pubmed: 28587670
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Lupus. 2012 Jul;21(8):855-64
pubmed: 22433915
Proteomics Clin Appl. 2015 Dec;9(11-12):1012-20
pubmed: 25824007
Autoimmun Rev. 2015 Aug;14(8):692-702
pubmed: 25888464
Clin Sci (Lond). 2017 Apr 25;131(8):653-671
pubmed: 28183811
Ann Rheum Dis. 2007 Dec;66(12):1661-8
pubmed: 17504842
J Am Soc Nephrol. 2005 Feb;16(2):383-91
pubmed: 15601747
Mol Biol Rep. 2010 Mar;37(3):1341-5
pubmed: 19319662
J Clin Invest. 2014 Jun;124(6):2307-14
pubmed: 24892704
Nucleic Acids Res. 2014 Jan;42(Database issue):D1253-60
pubmed: 24225319
J Am Soc Nephrol. 2004 Feb;15(2):241-50
pubmed: 14747370
Arthritis Res Ther. 2006;8(6):R162
pubmed: 17062137
Biochim Biophys Acta. 2010 Apr;1804(4):653-61
pubmed: 19836472
Nephrol Dial Transplant. 2015 Jul;30(7):1097-103
pubmed: 25248362
J Dermatol. 2017 Jan;44(1):18-22
pubmed: 27345569
BMB Rep. 2013 Apr;46(4):230-5
pubmed: 23615266
Am J Med Sci. 2010 Mar;339(3):230-2
pubmed: 20090510
Lupus Sci Med. 2014 Apr 01;1(1):e000013
pubmed: 25396061
Am J Pathol. 2006 Jun;168(6):1779-92
pubmed: 16723695
J Am Soc Nephrol. 2014 Nov;25(11):2483-98
pubmed: 24790181
Mol Cell Biol. 2003 Aug;23(15):5376-87
pubmed: 12861023
Nephrol Dial Transplant. 2011 Sep;26(9):2752-60
pubmed: 21378392
Am J Pathol. 2014 Jun;184(6):1727-39
pubmed: 24726496
J Autoimmun. 2015 Jul;61:54-61
pubmed: 26071203
Arthritis Rheumatol. 2014 Feb;66(2):397-406
pubmed: 24504812
J Clin Invest. 1996 Jun 1;97(11):2499-508
pubmed: 8647942
Mol Cell Proteomics. 2012 Apr;11(4):M111.008755
pubmed: 22159597
J Rheumatol. 2003 Jul;30(7):1495-504
pubmed: 12858447
Arthritis Rheum. 2006 Jan;54(1):343-55
pubmed: 16385526
Rheumatology (Oxford). 2011 Jan;50(1):47-59
pubmed: 20864496
J Am Soc Nephrol. 2010 Nov;21(11):1912-27
pubmed: 20847146
J Biol Chem. 2013 Sep 27;288(39):28163-79
pubmed: 23928303
Kidney Int. 2020 Jan;97(1):163-174
pubmed: 31901340
Am J Kidney Dis. 2020 Aug;76(2):265-281
pubmed: 32220510

Auteurs

Dawn J Caster (DJ)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Erik A Korte (EA)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Michael L Merchant (ML)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Jon B Klein (JB)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA.

Michelle T Barati (MT)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Ami Joglekar (A)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Daniel W Wilkey (DW)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Susan Coventry (S)

Pathology Department, Norton Children's Hospital, Louisville, KY 40202, USA.

Jessica Hata (J)

Pathology Department, Norton Children's Hospital, Louisville, KY 40202, USA.

Brad H Rovin (BH)

Department of Medicine, The Ohio State University, Columbus, OH 43210, USA.

John B Harley (JB)

Center for Autoimmune Genomics and Etiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
US Department of Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.

Bahram Namjou-Khales (B)

Center for Autoimmune Genomics and Etiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.

Kenneth R McLeish (KR)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

David W Powell (DW)

Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Classifications MeSH