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

Scientific paper - Original scientific paper

• Author: Alan Šućur
• Author: Zrinka Jajić
• Author: Marina Ikić Matijašević
• Author: Asja Stipić Marković
• Author: Darja Flegar
• Author: Nina Lukač
• Author: Tomislav Kelava
• Author: Nataša Kovačić
• Author: Danka Grčević
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Anatomy and Clinical Anatomy)
• Author's institution: University of Zagreb; School of Medicine; (Department of Physical Medicine and General Rehabilitation)
• Author's institution: University of Zagreb; School of Medicine; (Department of Physiology and Immunology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Physical Medicine and Rehabilitation

Abstract (english)

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.
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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.
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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.
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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.

• Keywords (english): Arthritis, Psoriatic; Arthritis, Rheumatoid; Humans; Spondylitis, Ankylosing; T-Lymphocyte Subsets; Tumor Necrosis Factor-alpha
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Clinical and experimental rheumatology
• Numbering: vol. 38, no. 5, pp. 903-916
• p-ISSN: 0392-856X
• e-ISSN: 1593-098X
• URN:NBN: urn:nbn:hr:105:029043
• Publication: 2020-10
• Document URL: https://www.clinexprheumatol.org/abstract.asp?a=14516
• Type of resource: Text
• Access conditions: Open access; Embargo expiration date: 2021-11-01
• Created on: 2021-05-24 07:57:22