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Please use this identifier to cite or link to this item: http://hdl.handle.net/11055/880
Title: Expansion and activation of distinct central memory T lymphocyte subsets in complex regional pain syndrome
Authors: Russo Marc
Fiore Nathan T
van Vreden Caryn
Bailey Dominic
Santarelli Danielle M
McGuire Helen M
Fazekas de St Groth Barbara
Austin Paul J
ANZCA/FPM Author: Russo, M
Keywords: Complex regional pain syndrome
CRPS
Lymphocytes
Dendritic cells
Citation: 18;16(1):63
Abstract: 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 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 We have shown expansion and activation of several distinct populations of central memory T lymphocytes in CRPS. The number of central memory CD8+ T cells was increased 2.15-fold; furthermore, this cell group had increased phosphorylation of NFkB and STAT1 compared to controls. Regarding central memory CD4+ T lymphocytes, the number of Th1 and Treg cells was increased 4.98-fold and 2.18-fold respectively, with increased phosphorylation of NFkB in both populations. We also found decreased numbers of CD1c+ myeloid dendritic cells, although with increased p38 phosphorylation. These changes could indicate dendritic cell tissue trafficking, as well as their involvement in lymphocyte activation. 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+ and CD8+ T lymphocytes with increased activation of pro-inflammatory signalling pathways may indicate ongoing inflammation and cellular damage in CRPS.
URI: http://hdl.handle.net/11055/880
DOI: 10.1186/s12974-019-1449-9
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/30885223
Journal Title: Journal of Neuroinflammation
Type: Journal Article
Affiliates: Hunter Pain Clinic
Genesis Research Services
Discipline of Anatomy & Histology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney
Ramaciotti Centre for Human Systems Biology, Charles Perkins Centre, The University of Sydney
Sydney Cytometry, Centenary Institute and the Charles Perkins Centre
Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney
Study/Trial: Study
Appears in Collections:Scholarly and Clinical

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