TYPE I INTERFERON STATUS AND CLINICAL MANIFESTATIONS IN A LARGE COHORT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

PV036 / #672 Poster Topic: AS04 - Biomarkers Background/Purpose Type I interferons (IFN) are pivotal in the pathogenesis of SLE, with studies showing high IFN gene signature (IGS) status associated with certain organ manifestations, autoantibody profiles, and disease severity. With novel medications targeting the interferon pathway, an enhanced understanding the IGS in patients with SLE is necessary. In this study, we investigated the differences between IGS levels in relation to clinical characteristics in a large cohort of patients with SLE. Methods Patients meeting 2019 EULAR/ACR classification criteria for SLE from a single center were included. Whole blood collected cross-sectionally was analyzed for IGS by the DxTerity assay, categorizing patients into IFN high or IFN low status. The SLICC/ACR damage index (SDI), antibody status, glucocorticoid use, and use of immunosuppressives were analyzed according to IFN status. Additionally, the SLEDAI-2K, SLEDAI-2KG, and clinical SLEDAI-2K were characterized cumulatively from 5 years prior to whole blood collection to last available visit, with adjusted mean SLEDAI (AMS) and AMS-G calculated from the previous 10 years and stratified based on IFN status. Results In total, 506 patients with a median age of 49.5 years (IQR 37.26-60.49) were included, with 91.5% female. Overall, 291 (57.5%) were IFN high and 215 (42.5%) were IFN low. The median disease duration was longer in the IFN low group (22.7 years, IQR 11.58-21.05) than in the IFN high group (14.06 years, IQR 7.90-24.71) (p<0.001). The median SLEDAI-2K score was higher in the IFN high group (2.0, IQR 0.00-4.00) then in the IFN low group (0.0, IQR 0.00-4.00) (<0.001), as was the SLEDAI-2KG (8.0, IQR 0.00-3.75 vs 6.0, IQR 0.00-2.00) (p<0.001) though the clinical SLEDAI-2K was not significantly different. Similar trends were seen with the cumulative AMS (3.94, SD=2.61 vs 3.27, SZD 2.47) (p=0.004) and AMS-G (5.36, SD=3.53 vs 4.41, SD=3.25) (p=0.002). There was no difference in the proportion of the SLEDAI-2K organ domains between the IFN high and low groups, other than the hematologic domain (IFN high 82.8% vs. IFN low 73.0% [p=0.011]). The SDI was similar between the 2 groups. More patients in the IFN high vs. low group had positive autoantibodies (79.7% vs 67% [p=0.002]), including Smith (56.7% vs 32.6% [p<0.001]), RNP (66.7% vs 49.3% [p<0.001]), Ro (67.4% vs 47.0% [p<0.001]), La (30.9% vs 17.2% [p=0.001]), chromatin (75.6% vs 41.9% [p<0.001]), dsDNA (61.2% vs 38.1% [p<0.001]) and ribosomal P (27.1% vs 7.9% [p<0.001]) autoantibodies. There were no differences in levels of C3 or lupus anticoagulant, but more patients in the IFN high group had low C4 and positive anticardiolipin. More patients with high IFN were on glucocorticoids (38.5%) then were patients with low IFN low status (27%) (p=0.009). More IFN high status patients were on immunosuppressive agents (185; 63.6%) vs the IFN low group (98; 45.6%) (p<0.001). Similar trends were seen in our inception cohort, defined as those patients evaluated within 1 year of diagnosis. Conclusions In this large cohort of patients with SLE, IGS status may help to predict overall disease severity as per SLEDAI-2K, SLEDAI-2KG, AMS, and AMS-G (though not the clinical SLEDAI-2K), use of glucocorticoids, and overall use of immunosuppressive therapy, and is associated with more autoantibody positivity. IFN level did not reliably predict presence of specific SLEDAI-2K organ domains or damage. More studies are needed to assess those clinical characteristics associated with an elevated IGS and to determined who may respond best to type I IFN targeted therapies.