Background/Purpose:

The AMP-RA network applies cutting edge technologies to the study of tissue obtained by ultrasound guided synovial biopsy from patients with rheumatoid arthritis (RA). Ultrasound provides objective joint level measures of synovial inflammation, including hypertrophy (greyscale ultrasound, GSUS) and hyperaemia (Power Doppler ultrasound, PDUS). Furthermore, ultrasound joint count assessments enable higher sensitivity for measurement of systemic disease activity compared to clinical joint assessments alone. We examined the relationship between joint level ultrasound variables and synovial histology in Phase I patients with active RA. we also validated ultrasound measures against conventional measures of disease activity.

Methods:

During Phase I of AMP-RA we recruited patients fulfilling clinician RA diagnosis, 1987 or 2010 ACR/EULAR RA criteria with at least one joint amenable to biopsy. Patients were required to have a CDAI≥10; patients receiving i.a. steroids in the previous 4 weeks, i.m. in the last 8 weeks or oral steroids >10mg were excluded. 12 joint extended ultrasound assessments of 10 MCPs and 2 wrist joints using four point semiquantitative GSUS and PDUS scales were performed alongside collection of standard RA disease activity measures including DAS28CRP domains. 12 joint ultrasound indices were calculated by summing 0-3 grades for all joints. GSUS and PDUS measures were also assessed in the biopsied joint prior to the procedure. Retrieved tissue was fixed, stained and paraffin embedded prior to sectioning and staining by H&E. Tissues were assessed for quality: Where 50% or more tissue fragments out of a minimum of 4 contained lining layer histology, tissues were Krenn scored for lining layer and inflammatory infiltrate, and qualitative assessment of tissue pathotype by three histologists. In parallel, tissues were enzymatically disaggregated and cell yield determined using trypan dye exclusion.

Results:

In 15 tissue samples meeting QC taken from wrist (5), knee (9) and MCP (1) joints, Greyscale ultrasound (GSUS) grade correlated with the Krenn index of cellular inflammation (p<0.01, r=0.65) and the Krenn lining layer score (p<0.05, r=0.52). Power Doppler Ultrasound (PDUS) grade failed to correlate with either histological measure (p=0.34, p=0.48 respectively). Tissues with higher USGS, but not USPD scores, were more likely to show a lymphocyte predominant histological pathotype than other patterns (p<0.05). There was no consistent relationship between GSUS or PDUS measures of synovitis and cell yield at tissue disaggregation. GSUS extended joint indices correlated with DAS28CRP, 28 swollen joint and tender joint counts (p<0.05, r=0.70; p<0.01, r=0.78; p<0.05, r=0.65), while PDUS extended joint indices correlated with DAS28CRP and 28 swollen joint counts (p<0.05, r=0.66; p<0.05 r=0.76).

Conclusion:

Ultrasound measures of synovial hypertrophy correlate with the complexity of joint infiltrates and lining layer thickness. There was an association between synovial hypertrophy and a lymphocyte predominant pathotype. Extended joint indices demonstrate validity when compared to existing clinical domains.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/histological-and-clinical-correlates-of-ultrasound-measures-of-joint-inflammation-analysis-of-ra-tissue-obtained-by-ultrasound-guided-biopsy-in-phase-1-of-the-accelerating-medicines-partnership-ra-ne/