The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis.
ACPA, anti-citrullinated protein/peptide antibodies
AHCPA, anti-homocitrullinated protein/peptide antibodies
Anti-citrullinated protein/peptide antibodies
Anti-homocitrullinated (carbamylated) protein/peptide antibodies
ConA, Concanavalin A
Cytokines
HomoCitFib, homocitrullinated fibrinogen
Mouse model
RA, rheumatoid arthritis
RF, rheumatoid factor
Rheumatoid arthritis
SI, stimulation index
Sex
Shared epitope
anti-CarP, anti-carbamylated protein antibodies
sc, subcutaneous
Journal
Journal of translational autoimmunity
ISSN: 2589-9090
Titre abrégé: J Transl Autoimmun
Pays: Netherlands
ID NLM: 101759413
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
03
2020
accepted:
02
04
2020
entrez:
4
8
2020
pubmed:
4
8
2020
medline:
4
8
2020
Statut:
epublish
Résumé
Rheumatoid Arthritis (RA) is more common and severe in women compared to men. Both women and men with RA express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated proteins or peptides. These autoantibodies are strongly linked with the HLA-DR4 gene. The objective of this study was to determine sex differences in immune responses to homocitrullinated antigens. We used a humanized animal model of RA, DR4-transgenic mice and immunized them with a homocitrullinated peptide called HomoCitJED. Immune responses in these mice were measured for splenocyte proliferation by tritiated thymidine incorporation, serum autoantibody production by ELISA and cytokine levels by multiplex. We found that T cell and antibody responses to homocitrullinated antigens were similar in male and female mice. However, we found sex differences in serum cytokine profiles with female mice having higher ratio of IL-1α to IL-5, suggesting imbalances in immune regulation. This is the first study to report that immune responses to homocitrullinated antigens can be differentiated by sex.
Identifiants
pubmed: 32743533
doi: 10.1016/j.jtauto.2020.100053
pii: S2589-9090(20)30020-4
pii: 100053
pmc: PMC7388343
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100053Informations de copyright
© 2020 The Author(s).
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Immunol. 2003 Jul 15;171(2):538-41
pubmed: 12847215
Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17372-7
pubmed: 21987802
N Engl J Med. 2011 Dec 8;365(23):2205-19
pubmed: 22150039
J Exp Med. 2008 Apr 14;205(4):967-79
pubmed: 18391064
J Rheumatol. 2009 May;36(5):887-92
pubmed: 19273455
Arthritis Rheum. 1998 Dec;41(12):2196-204
pubmed: 9870876
Arthritis Rheumatol. 2017 Dec;69(12):2292-2302
pubmed: 28853240
PLoS One. 2015 Aug 24;10(8):e0135327
pubmed: 26301589
J Exp Med. 2006 Feb 20;203(2):275-80
pubmed: 16476768
Rheumatology (Oxford). 2019 Jan 1;58(1):149-153
pubmed: 30204896
J Rheumatol. 2018 Mar;45(3):302-309
pubmed: 29196382
Arthritis Rheum. 2008 Sep 15;59(9):1241-8
pubmed: 18759316
Nat Rev Rheumatol. 2019 Jan;15(1):9-17
pubmed: 30341437
Int Immunopharmacol. 2019 Sep;74:105675
pubmed: 31177017
J Autoimmun. 2012 May;38(2-3):J282-91
pubmed: 22225601
Ann Rheum Dis. 2000 Nov;59 Suppl 1:i103-8
pubmed: 11053099
Nat Commun. 2016 Jun 07;7:11596
pubmed: 27273006
Arthritis Res Ther. 2018 Jul 20;20(1):150
pubmed: 30029616
Ann Med. 2014 Aug;46(5):304-10
pubmed: 24813459
J Rheumatol. 2014 Dec;41(12):2361-9
pubmed: 25274884
J Exp Med. 2003 Dec 15;198(12):1951-7
pubmed: 14662908
J Autoimmun. 2018 May;89:75-81
pubmed: 29242008
Arthritis Rheum. 2007 Jan;56(1):69-78
pubmed: 17195209
Proc Soc Exp Biol Med. 1948 May;68(1):1-6
pubmed: 18863659
J Autoimmun. 2010 Aug;35(1):1-9
pubmed: 20061120
Arthritis Rheum. 2005 Apr 15;53(2):241-8
pubmed: 15818655
Br Med J. 1979 Jul 14;2(6182):97-9
pubmed: 111762
J Rheumatol. 2014 Feb;41(2):270-9
pubmed: 24429169
J Clin Rheumatol. 2012 Aug;18(5):259-60
pubmed: 22832285
Curr Opin Rheumatol. 2017 Jan;29(1):57-64
pubmed: 27755123
Nat Rev Rheumatol. 2013 Apr;9(4):252-6
pubmed: 23090510
Arthritis Rheumatol. 2014 Apr;66(4):786-93
pubmed: 24757131
Arthritis Rheum. 2011 Dec;63(12):3818-23
pubmed: 21953289
Arthritis Res Ther. 2009;11(1):R7
pubmed: 19144159