SLE stratification based on BAFF and IFN-I bioactivity for biologics and implications of BAFF produced by glomeruli in lupus nephritis.
B-cell activating factor (BAFF)
IFN-I
LN
SLE
glomerular macrophages
Journal
Rheumatology (Oxford, England)
ISSN: 1462-0332
Titre abrégé: Rheumatology (Oxford)
Pays: England
ID NLM: 100883501
Informations de publication
Date de publication:
02 05 2023
02 05 2023
Historique:
received:
11
07
2022
accepted:
03
09
2022
medline:
3
5
2023
pubmed:
13
9
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
B-cell activating factor (BAFF) is implicated in SLE pathogenesis. Blocking BAFF signalling has contributed to reducing glucocorticoid dosage and preventing organ damage. However, clinical characteristics of patients who may benefit from this therapy are not yet fully elucidated. Therefore, we identified patients with high BAFF-bioactivity to investigate their clinical characteristics and BAFF-producing cells. We established the reporter cell for BAFF and investigated the clinical characteristics of SLE patients with high BAFF-bioactivity. We identified BAFF-expressing kidney cells using publicly available scRNA-seq data and immunohistological analysis. SLE patients were stratified based on the bioactivity of BAFF and type-I IFN (IFN-I) to identify associated characteristic clinical manifestations. SLE patients, especially patients with LN, had significantly higher serum BAFF-bioactivity than healthy controls (HC) and non-LN patients. Additionally, single-cell-RNA-seq data and immunohistological analysis of kidney samples from LN patients revealed that BAFF is expressed in glomerular macrophages and mesangial cells. Notably, BAFF bioactivity was elevated in the urine of LN patients compared with that of non-LN patients, while no IFN-I bioactivity was detected in the urine. Furthermore, SLE stratification based on bioactivities of serum BAFF and IFN-I revealed the clinical characteristics of patients: high BAFF represented patients with LN and high IFN-I represented patients with blood and skin manifestations. Monitoring urinary BAFF-bioactivity may be valuable in diagnosing LN. Furthermore, stratification based on serum BAFF and IFN-I bioactivities may allow the identification of appropriate patients for biologics targeting BAFF and IFN-I.
Identifiants
pubmed: 36094336
pii: 6696196
doi: 10.1093/rheumatology/keac528
pmc: PMC10152287
doi:
Substances chimiques
Biological Products
0
B-Cell Activating Factor
0
Interferon Type I
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1988-1997Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.
Références
Immunol Rev. 2019 Mar;288(1):136-148
pubmed: 30874345
Arthritis Rheumatol. 2017 Feb;69(2):376-386
pubmed: 28130918
Korean J Intern Med. 2018 Mar;33(2):284-289
pubmed: 29320847
N Engl J Med. 2020 Sep 17;383(12):1117-1128
pubmed: 32937045
Nat Immunol. 2015 Jul;16(7):755-65
pubmed: 26006014
Ann Rheum Dis. 2018 Oct;77(10):1507-1515
pubmed: 29945921
Rheumatology (Oxford). 2020 Dec 5;59(Suppl5):v12-v18
pubmed: 32911542
Ann Rheum Dis. 2011 Oct;70(10):1857-65
pubmed: 21798884
Curr Dir Autoimmun. 2005;8:243-65
pubmed: 15564724
N Engl J Med. 2017 Apr 27;376(17):1615-1626
pubmed: 28445677
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Trends Mol Med. 2017 Jul;23(7):615-635
pubmed: 28623084
J Transl Autoimmun. 2020 Feb 13;3:100042
pubmed: 32743523
J Immunol. 2007 May 15;178(10):6624-33
pubmed: 17475894
Science. 1982 Apr 23;216(4544):429-31
pubmed: 6176024
Arthritis Res Ther. 2020 May 4;22(1):102
pubmed: 32366280
N Engl J Med. 2005 Dec 15;353(24):2550-8
pubmed: 16354891
Transl Res. 2015 Feb;165(2):296-305
pubmed: 25468480
Nat Rev Drug Discov. 2021 Mar;20(3):179-199
pubmed: 33324003
Blood. 2011 Aug 4;118(5):1305-15
pubmed: 21543762
Nat Rev Immunol. 2002 Jul;2(7):465-75
pubmed: 12094221
Arthritis Rheum. 2012 Aug;64(8):2677-86
pubmed: 22553077
Front Cell Dev Biol. 2020 Nov 06;8:577662
pubmed: 33240880
Nat Rev Immunol. 2021 Apr;21(4):209-220
pubmed: 33024284
Nat Rev Dis Primers. 2016 Jun 16;2:16039
pubmed: 27306639
J Am Soc Nephrol. 2004 Feb;15(2):241-50
pubmed: 14747370
Rheumatology (Oxford). 2007 Jul;46(7):1083-6
pubmed: 17500077
J Immunol. 2001 Jan 1;166(1):6-10
pubmed: 11123269
Nat Immunol. 2019 Jul;20(7):915-927
pubmed: 31110316
N Engl J Med. 2020 Jan 16;382(3):211-221
pubmed: 31851795
JCI Insight. 2018 Sep 6;3(17):
pubmed: 30185675
Nat Commun. 2018 May 1;9(1):1758
pubmed: 29717110
Arthritis Rheum. 1996 Mar;39(3):363-9
pubmed: 8607884
Ann Rheum Dis. 2018 Mar;77(3):355-363
pubmed: 29295825
Arthritis Rheum. 1997 Sep;40(9):1725
pubmed: 9324032
Brain. 2008 Jun;131(Pt 6):1455-63
pubmed: 18474519
Arthritis Rheum. 2001 Jun;44(6):1313-9
pubmed: 11407690
Immunity. 2018 Oct 16;49(4):725-739.e6
pubmed: 30314758
J Exp Med. 2007 Aug 6;204(8):1959-71
pubmed: 17664289
Nat Rev Rheumatol. 2020 May;16(5):255-267
pubmed: 32203285
Lupus. 2016 Apr;25(4):346-54
pubmed: 26385220
Arthritis Rheum. 2006 Jan;54(1):192-201
pubmed: 16385515
Arthritis Res Ther. 2006;8(2):R51
pubmed: 16507175
J Immunol. 2015 Sep 1;195(5):1933-7
pubmed: 26297793
Nat Immunol. 2019 Jul;20(7):902-914
pubmed: 31209404
Cell. 2016 Apr 21;165(3):551-65
pubmed: 27040498
Nat Rev Immunol. 2009 Jul;9(7):491-502
pubmed: 19521398
Clin Transl Immunology. 2019 Apr 21;8(4):e01047
pubmed: 31024730
Arthritis Rheumatol. 2017 Oct;69(10):2029-2037
pubmed: 28605137