Abstract
Objectives: Immune 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. Design: Blood 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. Results: Expected 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. Conclusions: Immune dysfunction may be present in OA beyond what appears related to ageing; this requires further investigation.
| Original language | English |
|---|---|
| Pages (from-to) | 1870-1878 |
| Number of pages | 9 |
| Journal | Osteoarthritis and Cartilage |
| Volume | 23 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2015 |
Funding
This work was supported by the IMI -funded project BeTheCure (No 115142-2 ), grant and Arthritis Research UK grants: 19545 (HERO) and 20083 ( Experimental Osteoarthritis Treatment Centre ). RR is funded by the Rose Hellaby Scholarship ( Guardian Trust ) New Zealand, The Royal Australasian College of Physicians (RACP)/ Australian Rheumatology Association & Starr Fellowship (Australia), New Zealand Rheumatology Association and Health Workforce New Zealand (contract number 242815/347837/00 ). MC was holder of University of Ottawa International Traveling Fellowship ( #31300 ). FP, PE and PC are part-funded by the National Institute for Health Research (NIHR) through the Leeds Musculoskeletal Biomedical Research Unit. This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Keywords
- Ageing
- Blood cell composition
- Cell subsets/phenotype
- OA
ASJC Scopus subject areas
- Rheumatology
- Biomedical Engineering
- Orthopedics and Sports Medicine