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Combined manual and automated immunophenotypisation identified disease-specific peripheral blood immune subpopulations in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis


1, 2, 3, 4, 5, 6, 7, 8, 9

 

  1. Croatian Institute for Brain Research, Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
  2. Clinical Hospital Center Sestre Milosrdnice, Department of Rheumatology, Physical Medicine and Rehabilitation, University of Zagreb School of Medicine, Zagreb, Croatia.
  3. Clinical Hospital Sveti Duh, Department of Clinical Immunology and Pulmology, Zagreb, Croatia.
  4. Clinical Hospital Sveti Duh, Department of Clinical Immunology and Pulmology, Zagreb, Croatia.
  5. Croatian Institute for Brain Research, Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
  6. Croatian Institute for Brain Research, Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
  7. Croatian Institute for Brain Research, Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
  8. Croatian Institute for Brain Research, Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.
  9. Croatian Institute for Brain Research, Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb, Croatia. danka.grcevic@mef.hr

CER12577
2020 Vol.38, N°5
PI 0903, PF 0916
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PMID: 31820725 [PubMed]

Received: 08/07/2019
Accepted : 07/10/2019
In Press: 20/11/2019
Published: 02/10/2020

Abstract

OBJECTIVES:
Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with abnormal immune cell functions. We combined manual and automated profiling in subpopulations of T-cells, B-cells and monocytes, in parallel to functional testing and clinical correlation.
METHODS:
Using flow cytometry, we analysed the expression of CCR4, CCR6 and CXCR5 on helper and cyotoxic T-cells, CD32B and CD86 on naïve and memory B-cells, and CCR1, CCR2, CCR4 and CXCR4 on monocytes in chronic high-disease activity patients to identify peripheral blood subpopulations. Cell activation, proliferative capability and osteoclastogenic effects were tested in vitro. Comparison with synovial compartment, clinical data and anti-TNF treatment were added to peripheral blood analysis.
RESULTS:
PsA had lower double-negative T-cell frequency, while RA had lower double-positive T-cell frequency and expanded Th1-like and cytotoxic T-cell subsets. CD32B expression was increased on naïve and memory B-cells in AS and associated with disease activity. CCR6+ and CXCR5+ cytotoxic T-cells and CD32B+ naïve and memory B-cells were highly enriched within the synovial compartment. T-cells and B-cells from AS exhibited enhanced activation and proliferation in vitro, whereas T-cell conditioned medium from RA produced an increased osteoclastogenic effect. CCR1 and CXCR4 were upregulated on osteoclastogenic monocyte subsets of RA, AS and PsA patients. Bioinformatic Citrus analysis identified additional T-cell, B-cell and monocyte clusters specifically associated with each disease.
CONCLUSIONS:
By combining manual and automated data analysis, our study revealed several disease-specific immune cell subpopulations, particularly cytotoxic T-cell subsets in RA and memory B-cell subsets in AS, which may serve as an indicator of active disease or possible therapeutic target.

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