AB1163 TYPE 1 INTERFERON SIGNATURE IN SYSTEMIC SCLEROSIS
Authors: Y. Allanore, A. Cauvet, M. Schwarz, J. Avouac
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Activation of the type 1 interferon (T1 IFN) pathway has been implicated in the pathogenesis of systemic sclerosis (SSc) by an increasing number of studies. Moreover, some preliminary data have shown the promise of measuring IFN signature to stratify SSc patients and to predict the outcomes in this very highly heterogeneous disease. <h3>Objectives:</h3> To measure T1 IFN pathway molecule serum concentrations in SSc and determine their association with baseline disease characteristics and also their predictive value on lung disease progression. <h3>Methods:</h3> We have used the MSD's ultrasensensitive assay for IFN-α2a determination and LUMINEX multiplex assay from R&amp;D System for the pro-inflammatory and chemokine panel determinations. We have included all consecutive patients admitted one-day in our department for an annual follow-up of the disease during the year 2019. We analysed all baseline characteristics and, in addition, thanks to the longitudinal follow-up of the patients we have determined for interstitial lung disease (ILD) the patients who progressed using the modified INBUILD trial criteria (symptoms, Forced Vital Capacity-FVC, HRCT and also the decision of the physician to escalade the treatment for ILD). <h3>Results:</h3> Two hundreds SSc patients have been included together with 29 matched healthy controls (blood donors). For SSc patients, the mean disease duration was 12±12 years, 84 (42%) had a diffuse cutaneous subset, median skin score was 4 (IQR:1-9), 67(33.5%) had some ILD changes on HRCT, 28(14%) had a restrictive syndrome defined by FVC below 70%, 8(4%) had pulmonary arterial hypertension, 83(41%) a history of digital ulcers, and 3(1.5%) a renal crisis. Regarding the ongoing therapies, 103 (51%) were receiving synthetic DMARDs and 42 (21%) biologic DMARDs. T1 IFN concentrations were higher in SSc patients compared to controls although not reaching significance (P=0.16) (Figure 1). We then used the 90th percentile of all values to get a proxy of normal values and this identified 62 SSc patients with a so-called IFN signature (Figure 1). As compared to controls, SSc patients had increased values of chemokines CCL8, CXCL10, CXCL19, CXCL11 and also interleukin-1 (all P&lt;0.0001). Moreover, higher levels of the aforementioned chemokines were detected in SSc individuals exhibiting IFN signature in contrast to those lacking this signature, as well as increased concentrations of IL1 and TNFα, underscoring an inflammatory profile. With regards to clinical characteristics; patients with IFN signature had more commonly a diffuse cutaneous subset (55% vs 35%; P=0.01) and exhibited a higher skin score (median 7 (1-11) vs 3 (0-8), p=0.023). ILD on HRCT was more common although not reaching significance (40% versus 30%; P=0.1), but FVC was significantly lower in patients with IFN signature (90±23 vs 99±25, p=0.02) (Figure 1). Corticosteroid or biologic DMARD use did not influence IFN signature but patients receiving synthetic DMARDDS had more commonly an IFN signature as compared to patients not receiving such treatment (63% vs 46%; P=0.03). The longitudinal analyses identified 19 patients has having a progressive ILD phenotype. A multivariate Cox regression analysis showed that age (P=0.01) and diffuse cutaneous subset (P=0.008) were predictors, that anti-topo were close to significance ((P=0.07) but IFN2a had no predictive value. <h3>Conclusion:</h3> Our results using serum ultrasensitive assay confirms the activation of IFN pathway in SSc with some relationships with both skin and lung involvements. IFN activation is linked with an inflammatory profile. IFN values were not predictive of ILD progression.REFERENCES: NIL. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Yannick Allanore Boehringer, Astra-Zeneca, Janssen, Prometheus, Topadur, Medsenic, Alpine ImmunoScience, MERCK, Anne Cauvet: None declared, Maximilian Schwarz: None declared, Jerome Avouac: None declared.