POS1165 INCREASED INTERFERON-I ACTIVITY IN COMBINATION WITH ELEVATED PERIPHERAL BLOOD PLASMABLASTS PREDICTS POOR OUTCOME IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: K. Speidel, Q. Cheng, L. Khodadadi, R. Biesen, F. Hiepe, T. Alexander
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is characterized by increased type I interferon (IFN) activity and elevated levels of peripheral blood plasmablasts (PB), both serving as established biomarkers for disease activity and severity. However, although being linked in immune dysregulation, these biomarkers have rarely been evaluated in combination for their prognostic value. <h3>Objectives:</h3> Here, we aimed to investigate the role of elevated IFN and peripheral blood PB levels in correlation to clinical disease measures, and to evaluate the prognostic value of these markers in SLE. <h3>Methods:</h3> SLE patients were investigated cross-sectionally by flow cytometry for the analysis of SIGLEC-1 on monocytes (as surrogate maker for IFN-I activity) and frequencies of circulating CD19<sup>pos</sup>CD20<sup>neg</sup>CD27<sup>++</sup>HLA-DR<sup>+</sup> PB from freshly isolated PBMCs between January 2015 and September 2019. In addition, these patients were prospectively followed for a median of 4.5 years (range 0.8 - 6.6 years), and investigated for the development of flares according to the SELENA-SLEDAI flare index (SFI). The study was approved by the local ethical committee (EA1/124/09). <h3>Results:</h3> 121 patients were included (89% female, median age 45.0 years), which could be separated into groups of SIGLEC<sup>low</sup>PB<sup>low</sup> (43.8%), SIGLEC<sup>high</sup>PB<sup>low</sup> (35.5%), SIGLEC<sup>low</sup>PB<sup>high</sup> (7.4%) and SIGLEC<sup>high</sup>PB<sup>high</sup> (13.2%). Compared to SIGLEC<sup>high</sup>PB<sup>low</sup>, patients with SIGLEC<sup>high</sup>PB<sup>high</sup> had a significantly higher disease activity (median SLEDAI of 8 vs. 4, p=0.001), lower rates of LLDAS (25.0% vs. 58.5%, p= 0.038), higher serum anti-dsDNA antibodies (26.9 vs. 200 IU/L, p&lt; 0.001), lower serum C3 levels (760 vs. 910mg/dl, p=0.018), and more frequent renal involvement (56.3% vs. 27.9%, p= 0.046). Throughout the observational period, a total of 385 flares occurred, comprising 337 mild/moderate and 48 severe flares. When standardized to flares per 10 observed years, the flare rate was significantly higher in the SIGLEC<sup>high</sup>PB<sup>high</sup> group (10.0 vs. 4.8, p=0.027), most pronounced for mild/moderate flares (8.4 vs. 3.9, p=0.013). This was associated with a higher cumulative glucocorticoid dosage (2181.6 vs. 1430.2 mg/year, p=0.043). Interestingly, there was no difference in the flare development in patients from the group of SIGLEC<sup>high</sup>PB<sup>low</sup> vs. SIGLEC<sup>low</sup>PB<sup>low</sup>. <h3>Conclusion:</h3> Our data indicate that SLE patients with a combination of IFN and humoral activity have a higher disease burden and poorer outcomes compared to patients with isolated IFN activity, which may have future implications in personalized therapeutic approaches. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>