Expansion and activation of distinct central memory T lymphocyte subsets in complex regional pain syndrome.
Adult
CD4-Positive T-Lymphocytes
/ pathology
CD8-Positive T-Lymphocytes
/ pathology
Complex Regional Pain Syndromes
/ complications
Cytokines
/ metabolism
Dendritic Cells
/ pathology
Female
Flow Cytometry
Humans
Lymphocyte Activation
Lymphocyte Count
Male
Middle Aged
Mood Disorders
/ etiology
Myeloid Cells
/ pathology
Pain Measurement
Statistics, Nonparametric
Central memory T lymphocytes
Complex regional pain syndrome
Mass cytometry
Myeloid dendritic cells
NFkB
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
18 Mar 2019
18 Mar 2019
Historique:
received:
30
01
2019
accepted:
28
02
2019
entrez:
20
3
2019
pubmed:
20
3
2019
medline:
16
7
2019
Statut:
epublish
Résumé
Complex regional pain syndrome (CRPS) is a debilitating condition where trauma to a limb results in devastating persistent pain that is disproportionate to the initial injury. The pathophysiology of CRPS remains unknown; however, accumulating evidence suggests it is an immunoneurological disorder, especially in light of evidence of auto-antibodies in ~ 30% of patients. Despite this, a systematic assessment of all circulating leukocyte populations in CRPS has never been performed. We characterised 14 participants as meeting the Budapest clinical criteria for CRPS and assessed their pain ratings and psychological state using a series of questionnaires. Next, we performed immunophenotyping on blood samples from the 14 CRPS participants as well as 14 healthy pain-free controls using mass cytometry. Using a panel of 38 phenotypic and activation markers, we characterised the numbers and intracellular activation status of all major leukocyte populations using manual gating strategies and unsupervised cluster analysis. We have shown expansion and activation of several distinct populations of central memory T lymphocytes in CRPS. The number of central memory CD8 These findings represent the first mass cytometry immunophenotyping study in any chronic pain state and provide preliminary evidence of an antigen-mediated T lymphocyte response in CRPS. In particular, the presence of increased numbers of long-lived central memory CD4
Sections du résumé
BACKGROUND
BACKGROUND
Complex regional pain syndrome (CRPS) is a debilitating condition where trauma to a limb results in devastating persistent pain that is disproportionate to the initial injury. The pathophysiology of CRPS remains unknown; however, accumulating evidence suggests it is an immunoneurological disorder, especially in light of evidence of auto-antibodies in ~ 30% of patients. Despite this, a systematic assessment of all circulating leukocyte populations in CRPS has never been performed.
METHODS
METHODS
We characterised 14 participants as meeting the Budapest clinical criteria for CRPS and assessed their pain ratings and psychological state using a series of questionnaires. Next, we performed immunophenotyping on blood samples from the 14 CRPS participants as well as 14 healthy pain-free controls using mass cytometry. Using a panel of 38 phenotypic and activation markers, we characterised the numbers and intracellular activation status of all major leukocyte populations using manual gating strategies and unsupervised cluster analysis.
RESULTS
RESULTS
We have shown expansion and activation of several distinct populations of central memory T lymphocytes in CRPS. The number of central memory CD8
CONCLUSIONS
CONCLUSIONS
These findings represent the first mass cytometry immunophenotyping study in any chronic pain state and provide preliminary evidence of an antigen-mediated T lymphocyte response in CRPS. In particular, the presence of increased numbers of long-lived central memory CD4
Identifiants
pubmed: 30885223
doi: 10.1186/s12974-019-1449-9
pii: 10.1186/s12974-019-1449-9
pmc: PMC6423749
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
63Commentaires et corrections
Type : ErratumIn
Références
J Immunol. 1999 Nov 1;163(9):5116-24
pubmed: 10528218
JAMA. 2001 Mar 21;285(11):1466-74
pubmed: 11255423
Mediators Inflamm. 2002 Feb;11(1):47-51
pubmed: 11930962
Science. 2002 Jun 7;296(5574):1873-6
pubmed: 12052961
Am J Psychiatry. 2002 Oct;159(10):1752-9
pubmed: 12359683
Nat Immunol. 2003 Jun;4(6):579-85
pubmed: 12730692
J Immunol. 2003 Nov 15;171(10):4984-9
pubmed: 14607893
Curr Psychiatry Rep. 2003 Dec;5(6):445-50
pubmed: 14609499
J Mich State Med Soc. 1951 Sep;50(9):1038-44
pubmed: 14874110
Neuroscience. 2004;129(3):767-77
pubmed: 15541898
J Neuroimmunol. 2005 May;162(1-2):184-9
pubmed: 15833374
Immunity. 2005 Apr;22(4):451-65
pubmed: 15845450
Pain. 2005 Aug;116(3):213-9
pubmed: 15964681
Brain Res Rev. 2006 Aug;51(2):240-64
pubmed: 16388853
Pain. 2006 Feb;120(3):244-66
pubmed: 16427199
Pain. 2006 Feb;120(3):235-43
pubmed: 16427737
Clin J Pain. 2006 Mar-Apr;22(3):235-9
pubmed: 16514322
J Exp Med. 2006 Apr 17;203(4):1045-54
pubmed: 16567390
Ann N Y Acad Sci. 2006 Jun;1069:62-76
pubmed: 16855135
Brain Behav Immun. 2007 Jul;21(5):668-76
pubmed: 17129705
Neurology. 2007 Jul 3;69(1):42-9
pubmed: 17606879
Pain. 2007 Nov;132(1-2):195-205
pubmed: 17890011
J Clin Invest. 2008 Jan;118(1):294-305
pubmed: 18060041
Neuroimmunomodulation. 2007;14(5):272-80
pubmed: 18239379
J Immunol. 2008 Feb 15;180(4):2158-64
pubmed: 18250422
Int Immunol. 2009 Jan;21(1):73-80
pubmed: 19050105
Nature. 2009 Mar 12;458(7235):211-4
pubmed: 19182777
Nat Immunol. 2010 Jan;11(1):83-9
pubmed: 19935657
J Immunol. 2010 Mar 15;184(6):2873-85
pubmed: 20154206
Immunity. 2010 Jul 23;33(1):35-47
pubmed: 20643337
Pain Med. 2010 Aug;11(8):1239-50
pubmed: 20704672
J Neuroimmunol. 2010 Dec 15;229(1-2):26-50
pubmed: 20870295
Pain. 2011 Feb;152(2):285-90
pubmed: 20947251
Clin Exp Immunol. 2011 Apr;164(1):108-17
pubmed: 21303362
Pharmacol Ther. 2011 May;130(2):226-38
pubmed: 21334376
Pain. 2011 Dec;152(12):2690-700
pubmed: 21816540
Adv Exp Med Biol. 2012;946:207-21
pubmed: 21948370
Nat Biotechnol. 2011 Oct 02;29(10):886-91
pubmed: 21964415
J Innate Immun. 2012;4(1):6-15
pubmed: 22086146
J Pain. 2012 Jan;13(1):10-20
pubmed: 22172450
Nat Immunol. 2012 May;13(5):481-90
pubmed: 22484734
Lancet Neurol. 2012 Jul;11(7):629-42
pubmed: 22710756
Pain. 2012 Sep;153(9):1916-31
pubmed: 22789131
Am J Hum Genet. 2012 Oct 5;91(4):713-20
pubmed: 23000145
J Neuroimmune Pharmacol. 2013 Jun;8(3):547-63
pubmed: 23188523
Autoimmun Rev. 2013 Apr;12(6):682-6
pubmed: 23219953
Neurology. 2013 Jan 1;80(1):106-17
pubmed: 23267031
Cytometry A. 2013 May;83(5):483-94
pubmed: 23512433
J Hand Surg Eur Vol. 2013 Jul;38(6):595-7
pubmed: 23778064
Int J Psychiatry Med. 2013;45(1):15-29
pubmed: 23805601
Pharmacol Rev. 2013 Dec 11;66(1):80-101
pubmed: 24335193
BMJ. 2014 Apr 28;348:g2631
pubmed: 24776533
PLoS One. 2014 Aug 14;9(8):e104883
pubmed: 25122126
Cell Rep. 2014 Sep 11;8(5):1318-27
pubmed: 25199826
Pain. 2014 Nov;155(11):2408-17
pubmed: 25250722
Sci Transl Med. 2014 Sep 24;6(255):255ra131
pubmed: 25253674
Front Plant Sci. 2014 Oct 31;5:578
pubmed: 25400647
Int J Rehabil Res. 2015 Jun;38(2):121-30
pubmed: 25426575
Cytokine. 2015 Feb;71(2):207-14
pubmed: 25461400
Cytometry A. 2015 Jul;87(7):636-45
pubmed: 25573116
J Neuroinflammation. 2015 Jan 21;12:12
pubmed: 25608762
Mediators Inflamm. 2015;2015:718201
pubmed: 25741131
Pain. 2015 Apr;156 Suppl 1:S94-103
pubmed: 25789441
J Neuroinflammation. 2015 May 20;12:96
pubmed: 25986444
Methods Mol Biol. 2015;1343:81-95
pubmed: 26420710
Front Immunol. 2015 Dec 16;6:632
pubmed: 26734003
Pain. 2016 Feb;157 Suppl 1:S2-6
pubmed: 26785152
J Neuroinflammation. 2016 Jan 19;13:14
pubmed: 26785976
Cytometry A. 2016 Jun;89(6):601-7
pubmed: 27061608
Brain Behav Immun. 2016 Aug;56:397-411
pubmed: 27118632
Cell. 2016 May 5;165(4):780-91
pubmed: 27153492
Adv Immunol. 2016;131:101-34
pubmed: 27235682
Nat Immunol. 2016 Jul 19;17(8):890-5
pubmed: 27434000
J Exp Med. 2016 Oct 17;213(11):2281-2291
pubmed: 27670591
Exp Neurol. 2017 Jan;287(Pt 1):14-20
pubmed: 27773721
Trends Immunol. 2017 Jan;38(1):5-19
pubmed: 27793571
Mediators Inflamm. 2017;2017:2764261
pubmed: 28634419
Expert Rev Proteomics. 2017 Oct;14(10):857-867
pubmed: 28803495
Sci Rep. 2017 Aug 15;7(1):8218
pubmed: 28811623
J Clin Invest. 2017 Sep 1;127(9):3210-3219
pubmed: 28862640
Sci Rep. 2017 Nov 28;7(1):16460
pubmed: 29184144
J Neuroinflammation. 2018 Apr 11;15(1):105
pubmed: 29642930
Curr Opin Immunol. 2018 Apr;51:187-196
pubmed: 29655022
J Pain. 2018 Oct;19(10):1102.e1-1102.e19
pubmed: 29684510
Med Hypotheses. 2018 Oct;119:41-53
pubmed: 30122490
Mol Pain. 2018 Jan-Dec;14:1744806918799127
pubmed: 30124090
Neuroscience. 2018 Oct 15;390:119-140
pubmed: 30125685
Inflamm Res. 2019 Jan;68(1):1-6
pubmed: 30155690
Mol Pain. 2018 Jan-Dec;14:1744806918815005
pubmed: 30392459
Eur J Pain. 2019 Apr;23(4):641-651
pubmed: 30620109
Science. 1993 Jun 18;260(5115):1808-10
pubmed: 8511589
J Hand Surg Br. 1998 Apr;23(2):147-50
pubmed: 9607647
Arch Phys Med Rehabil. 1998 Dec;79(12):1549-52
pubmed: 9862298