Abstract
SummaryObjectivesImmune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored whether abnormalities in the blood immune cell composition are present in OA, beyond defects typically associated with ageing.DesignBlood was collected from 121 healthy controls (HC) and 114 OA patients. Synovial biopsies were obtained from another 52 OA patients. Flow cytometry was used to establish the frequencies of lineage subsets, naïve, memory and regulatory T and B-cells, cells with an abnormal phenotype related to inflammation (IRC) and memory-like CD8+ T-cells. Multivariate analysis of covariance (MANCOVA) was used to determine whether the relative subset frequencies differed between HC and OA, controlling for age.ResultsExpected histology and T/B-cell infiltration were observed.Following age adjusted analysis, we confirmed the lack of age association in HC for CD4+, B, NK and NKT cells but a negative trend for CD8+ T-cells. In OA, CD4+ T-cell and B-cell frequency were lower compared to HC while CD8+ T-cell frequencies were higher. CD8+ memory-like cells were more likely to be found in OA (odds ratio = 15). Increased CD8+ IRC frequencies were also present in OA. The relationship between age and CD4+ or CD8+ naïve T-cells in HC were changed in OA while the age relationships with memory cells were lost. The increase in CD4+ Treg with age was also lost in OA. B-cells showed limited evidence of disturbance.ConclusionsImmune dysfunction may be present in OA beyond what appears related to ageing; this requires further investigation.
Highlights
Ageing is a complex phenomenon involving several human systems, simultaneously interacting at different levels[1]
Visual Analogue Score (VAS) was directly associated with the synovitis score
CD8þ T-cell phenotypes Memory like CD8þ T-cells were not present in all individuals (n 1⁄4 90 combing healthy controls (HC) and OA) and were analysed separately. These cells were more likely to be found in OA patients (71.7%; 71/99) than in HC (26.0%; 19/73) having adjusted for age [OR 1⁄4 14.91 (5.40, 41.18); P < 0.001]
Summary
Ageing is a complex phenomenon involving several human systems, simultaneously interacting at different levels[1]. It affects cells, tissues and whole organs; it diminishes homeostasis and increases vulnerability[2]. Many pathways, including the immune a Current address: Rheumatology and Immunology Department, Christchurch Hospital, Private Bag 4710, Christchurch 8140, New Zealand. F. Ponchel et al / Osteoarthritis and Cartilage 23 (2015) 1870e1878 response in ageing represents a major potential contributor to age-related conditions. Many of the age-related and inflammation-prone pathways may be involved in OA. Innate immune responses to calcium crystal deposition have been reported to activate the inflammasome pathway[20]
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