THU0060 ELEVATED SYNOVIAL MUC1 EXPRESSION IS ASSOCIATED WITH JOINT DAMAGE AND ONE-YEAR RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS
Authors: Yaoyao Zou, Jun Jing, Jiale Qin, Feng Zhou, Ting Liu, Jun-Wei Wang, Jianzi Lin, Lie Dai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The tumor-like transformation of synovium, especially the lining layer, play a critical role in joint damage in rheumatoid arthritis (RA) by forming aggressive and invasive rheumatoid pannus, but the underlying mechanisms remains unknown. Mucin1(MUC1), an O-glycosylated protein participating in forming protective mucous barriers on epithelial surfaces and intracellular signaling, has been found aberrantly expressed in many cancers and implicated in tumor progression and metastasis. However, the expression of MUC1 in synovium and its role in RA is unclear. <h3>Objectives</h3> We aimed to investigate the expression of MUC1 in RA synovium and its correlation with joint destruction in RA patients. <h3>Methods</h3> Synovial tissue (ST) were sampled by Parker-Pearson needle biopsy from 67 RA patients who had completed one year follow-up from a prospective RA cohort <sup>[1]</sup>. ST from 13 patients with orthopedic arthropathies (Orth. A) with arthroplasty or arthroscopy were used as control. Expression of MUC1 in ST was assessed by immunohistochemistry (IHC). Radiographic assessments of hand/wrist at baseline and month 12 were performed with the Sharp/van der Heijde-modified sharp score. Radiographic joint damage (RJD) was defined as total modified Sharp score (mTSS) &gt;10. Radiographic progression (RP) was defined as a change of mTSS more than 0.5 units. <h3>Results</h3> 1. Both nuclear and cytoplasmic MUC1 expression were observed in lining and sublining cells of synovium. The percentage of MUC1+ lining cells was significantly higher in RA (median 65.4%, IQR 53.6%∼73.2%) than that in Orth. A (median 43.1%, IQR 3.4%∼ 68.4%, <i>P</i> &lt;0.05). 2. Thirty-five (52%) RA patients showed RJD at baseline and their MUC1expression in lining layer was significantly enhanced compared with RA patients without RJD (median 69.6%, IQR64.5%∼76.8% vs. median 58.9%, IQR 39.8%∼67.9%, <i>P</i> &lt;0.01). Spearman's rank order correlation test showed significantly positive correlations between the percentage of MUC1+ lining cells with mTSS, joint space narrowing (JSN) subscore and joint erosion (JE) subscore at baseline (<i>r</i> =0.303∼0.426, all <i>P</i> &lt; 0.05). 3. Furthermore, twenty-two(33%) patients suffered from one-year RP and they showed significantly higher percentage of MUC1+ lining cells than non-progressive patients (median 71.2%, IQR 55.2%∼75.2 vs. median 64.1%, IQR 55.2%∼75.2%, <i>r</i> &lt; 0.01). The percentage of MUC1+ lining cells was positively correlated with mTSS, JSN and JE subscores at month 12 (<i>r</i> =0.310∼0.405, all <i>P</i> &lt; 0.05). ROC curve analysis showed that the tradeoff value of MUC1+ lining cells for predicting one-year RP was 69% with sensitivity 72% and specificity 71% (AUC=0.661, 95%CI∼0.516∼0.805, P=0.034). Univariate logistic regression analysis showed that high MUC1+ lining cells was a significant predictor of one-year radiographic progression (OR: 5.893, 95%CI: 1.934∼17.956, P=0.002). <h3>Conclusion</h3> Our data showed elevated MUC1expression in RA synovial lining cells was positively correlated with joint damage and predicted one-year radiographic progression, which imply that MUC1 might be involved in the pathogenesis of RA joint destruction. <h3>Reference</h3> [1] Chen Y, et al. Deleterious role of hepatitis B virus infection in therapeutic response among patients with rheumatoid arthritis in a clinical practice setting: a case-control study. Arthritis Research &amp; Therapy. 2018, 20(1). <h3>Acknowledgement</h3> This work was supported by National Natural Science Foundation of China (grant no. 81671612 and 81801605), Guangdong Natural Science Foundation (grant no. 2018A030313690 and 2017A030313576). <h3>Disclosure of Interests</h3> None declared