THU0070 The transcription factors ikaros and aiolos are expressed in the synovial membrane of early rheumatoid arthritis patients in association with synovial lymphoid aggregates
Authors: F. Rivellese, M. Congia, D. Mauro, M. Bombardieri, M. Lewis, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IKZF1 (Ikaros) and IKZF3 (Aiolos) are transcription factors acting as regulators of the immune system development. Specifically, they are essential for the maturation, differentiation and survival of B cells. Polymorphisms of IKZF1 and 3 have been linked to systemic autoimmunity, and they are being explored as therapeutic targets in Systemic Lupus Erythematosus. However, their involvement in other autoimmune diseases is currently unknown. <h3>Objectives</h3> To evaluate the expression of IKZF1 and 3 in the synovia of patients with early Rheumatoid Arthritis (RA) naïve to treatment, in correlation with the clinical phenotype, including treatment response. <h3>Methods</h3> DMARD-naïve patients with early (&lt;12 months) RA (n=41) fulfilling the 2010 ACR/EULAR criteria were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Sections of paraffin embedded synovial tissue obtained by ultrasound-guided synovial biopsy were stained by immunohistochemistry (IHC) for IKZF1 and IKZF3, and a semi-quantitative score (0–3) was used to classify patients (IKZF1 +ve or IKZF3 +ve cells/visual field &lt;5 =0; 5–20=1; 20–50=2;&gt;50=3). Sequential sections were stained by IHC for immune cells and patients were categorised into 3 synovial pathotypes according to the following criteria: i) Lymphoid (L) presence of grade 2–3 CD20 +aggregates, (CD20 ≥2) and/or CD138 &gt;2; ii) Myeloid (M) CD68SL≥2, CD20 ≤1 and/or CD3 ≥1, CD138 ≤2 and iii) Fibroid (F) CD68SL&lt;2 and CD3, CD20, CD138 &lt;1. <h3>Results</h3> Ikaros and Aiolos were expressed in the synovia of 43.1% and 56.7% of early RA patients, respectively. IKZF1 +ve patients (defined as IKZF1 score ≥2) showed a higher prevalence of a lymphoid pathotype (9/9 in IKZF1 +ve vs 4/22 in IKZF1-ve, p&lt;0.001) and a higher prevalence of ACPA (9/9 vs 13/22, p=0.04) and RF (9/9 vs 12/22, p=0.02). IKZF3 +ve patients showed a similar association with local and systemic inflammation and autoantibody positivity. As shown in table 1, ikaros and aiolos synovial scores were significantly correlated with synovial cell infiltrate and systemic inflammation. Remarkably, ikaros showed a significant correlation with the baseline Sharp score. Accordingly, patients with high expression of Ikaros (sq score ≥2) had a significantly higher Sharp score (mean ±SD 4.75±3.3 vs 1.33±2.54, p=0.008). <h3>Conclusions</h3> Here, we show the expression of the transcription factors Ikaros and Aiolos in the synovia of early RA patients in correlation with lymphoid aggregates and systemic inflammation, and, for Ikaros, with baseline radiographic erosions. While additional analyses are needed in order to confirm the expression and function of ikaros and aiolos by synovial immune cells, our preliminary work suggest that they might be relevant in the pathogenesis of RA and therefore be considered as therapeutic targets in a subset of patients. <h3>Disclosure of Interest</h3> None declared