To Örebro University

oru.seÖrebro University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
ABERRANT PHENOTYPE OF CIRCULATING ANTIGEN PRESENTING CELLS IN GIANT CELL ARTERITIS AND POLYMYLAGIA RHEUMATICA
Örebro University, School of Medical Sciences. Orebro Univ, Fac Med & Hlth, Orebro, Sweden..ORCID iD: 0000-0002-4250-0930
University Medical Center Groningen, Rheumatology and Clinical Immunology, Groningen, Netherlands.
University Medical Center Groningen, Rheumatology and Clinical Immunology, Groningen, Netherlands.
University Medical Center Groningen, Rheumatology and Clinical Immunology, Groningen, Netherlands.
Show others and affiliations
2023 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 82, no Suppl. 1, p. 1071-1071, article id POS1434Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping diseases occurring exclusively in people older than 50 years. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. In GCA tissues, DCs may be prone to activation, leading to chemokine production and recruitment of CD4+ T-cells and monocytes to the arterial wall. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.

Objectives: We aimed to investigate the phenotype of the circulating monocytes and DCs in GCA and PMR patients.

Methods: APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). Using a 13-colour panel, we identified three monocyte subsets: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14lowCD16+) monocytes. DC subsets were subdivided in CD303+CD11c- plasmacytoid DCs (pDCs), CD11c+CD141+ conventional DCs (cDC1) and CD11c+CD1c+ conventional DCs (cDC2). Each of these subsets was analysed for expression of pattern recognition receptors (Toll-like receptor 4 (TLR4), TLR2) and activation markers (CD86, Programmed Death- Ligand 1 (PD-L1), CD40, HLA-DR, CD11c) by assessing the mean-fluorescence intensity of these markers. Data were analysed by conventional gating strategies and by unsupervised tSNE.

Results: GCA and PMR patients displayed a monocytosis, which was due to increases in classical and intermediate monocyte counts, whereas the proportion of non-classical monocytes was reduced. Intermediate monocytes of GCA patients had significantly higher TLR2 expression, a similar trend was observed in non-classical monocytes of GCA and PMR patients. A divergent pattern was observed in the expression of activation markers on classical versus non-classical monocytes: classical monocytes of GCA/PMR patients appeared to be less activated, whereas non-classical monocytes showed an increased marker expression compared to HCs (Figure 1). Even though no differences were observed in DC counts in the peripheral blood, cDC2 counts correlated negatively with CRP levels (r=-0.60 for GCA, r=-0.55 for PMR).

Conclusion: Circulating non-classical monocytes, but not DCs, display an activated phenotype in GCA and PMR patients at diagnosis. These cells are thought to be pro-inflammatory, representing the end stage of monocyte maturation in the blood. In contrast, classical monocytes show reduced expression of activation markers in GCA and PMR patients, potentially signalling either an immature or exhausted phenotype. Shown is the mean fluorescence intensity (MFI) of CD11c on the surface of monocyte subsets and CD1c+ conventional dendritic cells (cDC2). Data are shown for patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR) and age-matched healthy controls (HCs), n=15 for each group. Statistics by Mann Whitney U. CD11c expression data for pDCs (no CD11c expression) and cDC1 (too small population) are not shown.

Place, publisher, year, edition, pages
HighWire Press , 2023. Vol. 82, no Suppl. 1, p. 1071-1071, article id POS1434
Keywords [en]
Innate immunity, Vasculitis
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:oru:diva-111553DOI: 10.1136/annrheumdis-2023-eular.3189ISI: 001107398703335OAI: oai:DiVA.org:oru-111553DiVA, id: diva2:1837904
Conference
European Congress of Rheumatology (EULAR 2023), Milan, Italy, May 31 - June 3, 2023
Available from: 2024-02-15 Created: 2024-02-15 Last updated: 2024-02-15Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Authority records

Reitsema, R.

Search in DiVA

By author/editor
Reitsema, R.
By organisation
School of Medical Sciences
In the same journal
Annals of the Rheumatic Diseases
Rheumatology and Autoimmunity

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 22 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf