Knee osteoarthritis phenotypes based on synovial fluid immune cells correlate with clinical outcome trajectories

  • M. Trajerova
    Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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  • E. Kriegova
    Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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  • Z. Mikulkova
    Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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  • J. Savara
    Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic

    Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic
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  • M. Kudelka
    Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic
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  • J. Gallo
    Address correspondence and reprint requests to: J. Gallo, Department of Orthopaedics, Palacký University Olomouc and University Hospital Olomouc, I.P. Pavlova 6, 775 15 Olomouc, Czech Republic.
    Department of Orthopaedics, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
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Published:September 17, 2022DOI:



      Knee osteoarthritis (KOA) is a highly heterogeneous disease encompassing a wide range of clinical phenotypes. Phenotypes based on immune cells and protein pattern in synovial fluid (SF) and their relationship to clinical trajectories have not been described.


      To assess phenotypes based on immune cells and protein pattern of SF in KOA.


      SF-derived immune cells were investigated in 119 patients with KOA using flow cytometry. Immune-phenotypes (iPhen) were determined by multivariate patient similarity network analysis and related to clinical trajectory (3–6 months post-sampling) along with protein pattern and macrophage chemokine receptors.


      Four iPhen were detected based on the distribution of T-lymphocytes, monocyte–macrophage lineage cells and activated CD8+ T-lymphocytes. The ‘activated’ phenotype (n = 17) had high T-lymphocytes but low monocyte–macrophage lineage cells and neutrophils, all highly activated, and showed improved symptoms in 70% patients. The ‘lymphoid progressive’ phenotype (n = 31) had high neutrophils, low lymphocytes and monocyte–macrophage lineage cells, low activation and was associated with lower pain levels. The ‘myeloid progressive’ phenotype (n = 35) had high NK and monocyte–macrophage lineage cells but low T-lymphocytes and activation. The ‘aggressive’ phenotype (n = 36) had high lymphocytes, macrophages, NK cells and neutrophils and high activation, and only 39% of patients improved during follow-up. Low CXCR4 and CCR7 expression on macrophages and high CXCL10 in SF were linked to improved clinical trajectory.


      We identified four immune-phenotypes that were associated with different clinical trajectories in KOA patients. How these phenotypes can be targeted therapeutically deserves further investigation.


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