Session Information
Date: Monday, November 9, 2015
Title: Biology and Pathology of Bone and Joint Poster I: Osteoarthritis Pathogenesis
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose:
Power doppler ultrasound provides joint level data on the risk of erosive progression in patients with inflammatory arthritis. Understanding the synovial tissue correlates of ultrasound variables may reveal factors that drive erosive disease. The purpose of this study was to examine the relationship between ultrasound variables, tissue histological variables and cytokine profiles in DMARD naïve inflammatory arthritis patients.
Methods:
Ultrasound guided synovial biopsies were obtained from patients with at least one clinically swollen joint at presentation to the Birmingham Early arthritis Cohort (BEACON) and followed for 18 months to confirm outcome as either rheumatoid arthritis fulfilling 2010 criteria (RA: n=29, median symptom duration 10 weeks), or spontaneously resolving disease (RES: n=9, median symptom duration 5 weeks). All patients underwent baseline ultrasound, clinical and serological assessment. Fractional Power Doppler pixel quantification (USPD) was performed using a custom Matlab application. Ultrasound Greyscale (USGS) synovial hypertrophy was graded on a 4 point semiquantitative scale. Synovial tissue histology variables were assessed by blinded pathologists. Synovial cellular populations were quantified by blinded cell counts of fluorescence stained tissue sections. Synovial mRNA expression of 119 cytokines was quantified using low density PCR array techniques.
Results:
Histological grading of leukocyte infiltrate complexity in biopsies correlated with USGS synovial hypertrophy (RA p<0.05, RA+RES combined p<0.01), but not USPD. Lining layer thickness did not correlate with USGS or USPD in any group. Neither infiltrate complexity nor lining layer thickness was significantly different between diagnostic groups. After correction for multiple comparisons, mRNA levels of key cytokines and chemokines were positively correlated with PDUS in RA, including IL-6 (p=0.007), IL-32 (p=0.0.025) and the chemokines CCL2 (p=0.007), CCL7 (p=0.0002), CCL8 (p=0.0161), CCL19 (p=0.024) and CXCL13 (p=0.045), while key mediators of low inflammation pathways were negatively correlated with PDUS, including IGFBP5 (P=0.048), Galectin-3 (P=0.002) , Galectin12 (P=0.043) and SFRP-1 (P=0.01). A similar pattern was seen in the RES group, and combining groups resulted in a total of 30 genes correlated with PD. Correlation of PDUS with CD68-positive joint counts in synovial biopsies revealed a positive relationship for combined groups (RA+RES p=0.03, RA alone P=0.05).
Conclusion:
Infiltrate complexity correlates most closely with the extent of synovial hypertrophy, rather than hyperaemia measured by PD. However US power doppler fraction correlates positively with key inflammatory macrophage related cytokines, chemokines, growth factors and tissue CD68 positive cell counts, providing an explanation for the link beween power doppler and joint damage.
To cite this abstract in AMA style:
Yeo L, Scheel-Toellner D, Ludwig C, Sahbudin I, Juarez M, Buckley C, Raza K, Filer A. Synovial Ultrasound Power Doppler Enhancement Reflects Multiple Cytokine Expression in Synovial Tissue, Distinguishing Distinct High Macrophage-Associated and Low Inflammation Profiles [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/synovial-ultrasound-power-doppler-enhancement-reflects-multiple-cytokine-expression-in-synovial-tissue-distinguishing-distinct-high-macrophage-associated-and-low-inflammation-profiles/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/synovial-ultrasound-power-doppler-enhancement-reflects-multiple-cytokine-expression-in-synovial-tissue-distinguishing-distinct-high-macrophage-associated-and-low-inflammation-profiles/