Autoreactive Plasmablasts After B Cell Depletion With Rituximab and Relapses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
04
09
2022
received:
24
07
2021
accepted:
11
10
2022
pmc-release:
01
05
2024
medline:
17
5
2023
pubmed:
26
10
2022
entrez:
25
10
2022
Statut:
ppublish
Résumé
Autoreactive B cells are responsible for antineutrophil cytoplasmic antibody (ANCA) production in ANCA-associated vasculitis (AAV). Rituximab (RTX) depletes circulating B cells, including autoreactive B cells. We aimed to evaluate changes and associations with relapse of the circulating autoreactive B cell pool following therapeutic B cell depletion in AAV. Sequential flow cytometry was performed on 148 samples of peripheral blood mononuclear cells from 23 patients with proteinase 3 (PR3)-ANCA-positive AAV who were treated with RTX for remission induction and monitored after stopping therapy during long-term follow-up in a prospective clinical trial. PR3 was used as a ligand to target autoreactive PR3-specific (PR3+) B cells. B cell recurrence was considered as the first blood sample with ≥10 B cells/μl after RTX treatment. At B cell recurrence, PR3+ B cell frequency among B cells was higher than baseline (P < 0.01). Within both PR3+ and total B cells, frequencies of transitional and naive subsets were higher at B cell recurrence than at baseline, while memory subsets were lower (P < 0.001 for all comparisons). At B cell recurrence, frequencies of B cells and subsets did not differ between patients who experienced relapse and patients who remained in remission. In contrast, the plasmablast frequency within the PR3+ B cell pool was higher in patients who experienced relapse and associated with a shorter time to relapse. Frequencies of PR3+ plasmablasts higher than baseline were more likely to be found in patients who experienced relapse within the following 12 months compared to those in sustained remission (P < 0.05). The composition of the autoreactive B cell pool varies significantly following RTX treatment in AAV, and early plasmablast enrichment within the autoreactive pool is associated with future relapses.
Identifiants
pubmed: 36281741
doi: 10.1002/art.42388
pmc: PMC10280646
mid: NIHMS1844052
doi:
Substances chimiques
Rituximab
4F4X42SYQ6
Antibodies, Antineutrophil Cytoplasmic
0
Myeloblastin
EC 3.4.21.76
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
736-747Subventions
Organisme : NIAID NIH HHS
ID : N01AI15416
Pays : United States
Organisme : NIAMS NIH HHS
ID : RC1 AR058303
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI109565
Pays : United States
Informations de copyright
© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
Références
JCI Insight. 2021 Nov 22;6(22):
pubmed: 34618687
Ann Intern Med. 2007 Nov 6;147(9):611-9
pubmed: 17975183
Arthritis Rheumatol. 2019 Mar;71(3):340-350
pubmed: 30277007
N Engl J Med. 2014 Nov 6;371(19):1771-80
pubmed: 25372085
Arthritis Res Ther. 2017 May 18;19(1):101
pubmed: 28521808
Rheumatology (Oxford). 2016 Jan;55(1):162-72
pubmed: 26320128
J Autoimmun. 2014 May;50:135-41
pubmed: 24703438
Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115-9
pubmed: 2161532
N Engl J Med. 2010 Jul 15;363(3):211-20
pubmed: 20647198
Blood. 2009 Dec 10;114(25):5173-81
pubmed: 19846886
Arthritis Rheumatol. 2016 Sep;68(9):2210-20
pubmed: 27059652
Arthritis Rheum. 2006 Feb;54(2):613-20
pubmed: 16447239
N Engl J Med. 2010 Jul 15;363(3):221-32
pubmed: 20647199
Clin J Am Soc Nephrol. 2010 Aug;5(8):1394-400
pubmed: 20498238
Front Immunol. 2019 Sep 24;10:2221
pubmed: 31608054
Sci Transl Med. 2013 Mar 6;5(175):175ra30
pubmed: 23467561
Arthritis Rheum. 2011 May;63(5):1237-45
pubmed: 21538313
J Autoimmun. 2017 Nov;84:122-131
pubmed: 28870527
Clin Exp Immunol. 2012 Sep;169(3):220-8
pubmed: 22861361
Nat Rev Dis Primers. 2020 Aug 27;6(1):71
pubmed: 32855422
Arthritis Rheumatol. 2021 Jan;73(1):121-131
pubmed: 32755035
Nat Rev Rheumatol. 2016 Oct;12(10):570-9
pubmed: 27464484
Clin Immunol. 2008 Apr;127(1):14-25
pubmed: 18191619
Autoimmun Rev. 2015 Nov;14(11):996-1004
pubmed: 26143354
J Clin Invest. 1974 Jan;53(1):240-6
pubmed: 4808638
Clin Vaccine Immunol. 2007 Jan;14(1):52-9
pubmed: 17050740
J Clin Lab Anal. 1991;5(4):255-61
pubmed: 1890539
Rheumatology (Oxford). 2012 Jan;51(1):100-9
pubmed: 22039267
J Allergy Clin Immunol. 2008 Jan;121(1):13-21; quiz 22-3
pubmed: 18206502
J Autoimmun. 2018 Sep;93:89-103
pubmed: 30054207
J Am Soc Nephrol. 2015 Mar;26(3):537-42
pubmed: 25324502
Ann Rheum Dis. 2015 Sep;74(9):1734-8
pubmed: 25854586
Arthritis Rheum. 2007 Sep;56(9):3044-56
pubmed: 17763423
Arthritis Rheum. 2012 Nov;64(11):3770-8
pubmed: 22730028
J Clin Invest. 1978 Apr;61(4):922-30
pubmed: 96133
Ann Rheum Dis. 2016 Jun;75(6):1170-6
pubmed: 26034045
Eur J Immunol. 2019 Jul;49(7):1107-1116
pubmed: 30893475
Ann Rheum Dis. 2017 Aug;76(8):1449-1457
pubmed: 28442530
J Immunol. 2009 May 15;182(10):5982-93
pubmed: 19414749
Ann Rheum Dis. 2021 Feb;80(2):176-184
pubmed: 32998865
Ann Rheum Dis. 2020 Sep;79(9):1243-1249
pubmed: 32581088
Arthritis Rheumatol. 2017 Dec;69(12):2338-2350
pubmed: 28881446
Arthritis Rheumatol. 2016 Jul;68(7):1700-10
pubmed: 26882078
N Engl J Med. 2013 Aug 1;369(5):417-27
pubmed: 23902481