Ab0559 Serum Mac-2 Binding Protein Glycosylation Isomer Levels Correlate With Disease Activity in Patients With Rheumatoid Arthritis, a Disease Associated With Type I Interferonopathy

Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that eventually leads to the destruction of cartilage and bone[1]. A type I interferon (INF-I) signature (ISG) is detectable in the peripheral blood of RA patients and may be present in the preclinical phase of the disease[2]. INF-Is have been implicated in the pathogenesis of RA. JAK inhibitors (Jakinibs) block the activation of the IFN pathway by inhibiting JAKs, resulting in a very promising therapeutic strategy for adults suffering from autoimmune, inflammatory and haematological diseases such as RA. We have shown that serum Mac-2BPGi (M2BP) levels are significantly elevated in patients with rheumatic diseases associated with type 1 interferonopathies, including rheumatoid arthritis, compared to healthy controls[3]. At present, the significance of M2BP in RA is unclear. Objectives: The aim of this study is to evaluate the utility of serum M2BP levels in patients with RA. Methods: This was a retrospective cross-sectional study. A total of 135 eligible RA patients were included in this study in our department's database from January to April 2020, excluding patients with neither RA disease activity nor laboratory data including M2BP. Serum levels of M2BP were measured using the HISCLÒ M2BP glycosylation isomer assay kit. Clinical remission was defined as a Simplified Disease Activity Index (SDAI) ≤ 3.3. Serum M2BP levels were categorised into tertiles (LOW, MID and HIGH). Results: The median age of patients was 67.0 (IQR: 57.0-73.0) years, and the median disease duration was 13.0 (9.0-6.5) years. The median SDAI was 2.02 (1.16-5.11) and the median Disease Activity Score 28-C-reactive protein (DAS28-CRP) was 1.61 (1.26-2.12). Of the 135 patients, 85 were in clinical remission (REM). There were no significant differences between the REM and non-REM groups in the proportion of methotrexate (MTX) use, biologics and JAK inhibitors use, but prednisolone (PSL) use and csDMARDs other than MTX were significantly higher in the non-REM group. Median serum M2BP levels were 0.85 cut-off index (C.O.I.) (0.63-1.18). M2BP was significantly correlated with SDAI and DAS28-CRP (r=0.230 and r=0.238, respectively). Serum M2BP tended to be lower in the SDAI remission group compared to the non-remission group (0.79 vs. 0.93); serum M2BP levels were significantly lower in the DAS28-CRP remission group compared to the non-remission group (0.80 vs. 1.07, p<0.02). The proportion of SDAI remission tended to decrease with increasing serum M2BP, whereas the proportion of DAS28-CRP remission significantly decreased with increasing serum M2BP. Multiple regression analysis of serum M2BP identified age and SDAI as independent factors. In this multiple regression analysis, treatment with biologics and JAKinib, excluding abatacept (ABT), tended to reduce M2BP compared to csDMARDs alone. The use of MTX and PSL also tended to reduce it. And treatment with JAKinibs tended to reduce M2BP more than the other treatments. Conclusion: The study showed that serum M2BP levels correlate with disease activity in rheumatoid arthritis as an independent factor. Previous studies have reported that serum M2BP correlates with type 1 interferon signalling in RA, and this study found a trend for JAKinibs treatment to reduce M2BP more than other treatments. Therefore, it has been suggested that serum M2BP may be a marker not only for the assessment of disease activity, but also for treatment selection and response in RA. REFERENCES: [1] Drossaers-Bakker KW, de BM, van ZD, et al. Arthritis Rheum 1999;42:1854–60. [2] Lubbers, J. et al. Ann. Rheum. Dis. 72, 776–780 (2013). [3] Yoshikawa T, Azuma K, Furukawa T, Tamura M, Hashimoto T, Morimoto M, et al. Ann Rheum Dis. 2021;80(Suppl 1):1181.1-1181. Acknowledgements: NIL. Disclosure of Interests: None declared.