OP0170 DECLINE IN FORCED VITAL CAPACITY (FVC) IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) WITH AND WITHOUT DYSPNOEA: DATA FROM THE SENSCIS TRIAL

Abstract

Background: Deficiency of adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory disease whose pathogenesis has not been clearly elucidated. Objectives: To investigate the role of vascular inflammatory factors in the patho-genesis of DADA2, to compare the vascular inflammation profiles of DADA2 patients with different phenotypes, and to compare DADA2 patients with classic polyarteritis nodosa (PAN). Methods: The study included eighteen DADA2 patients, ten PAN patients, and eight healthy controls. Plasma levels of sST2, sRAGE, Tie-2, sCD40L, Tie-1, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, MCP-1 were studied by cytometric bead-based multiplex assay panel. Results: Among the DADA2 patients, five had hematological manifestations, 13 had vasculitic findings, and accompanying immunological findings were present in seven patients. Nine patients had neurological findings, five of whom had neu-ropathy. Hematological findings were Diamond-Blackfan anemia-like phenotype in four patients and bicytopenia (anemia and thrombocytopenia) in one patient. Disease characteristics of DADA2 and PAN patients revealed that neurolog-ical involvement and livedo reticularis were more frequent in DADA2 patients (p=0.034 and p=0.009, respectively), while myalgia was more common in PAN patients (p:0.001). Plasma levels of Tie-1 and sFlt-1 were higher in the overall DADA2 patients compared to healthy controls and PAN patients (p<0.001 and p=0.004, respectively). DADA2 patients with PAN-like features had higher sRAGE, Tie-2, and TNF-α levels compared to PAN patients (p=0.013, p=0.003, and p=0.001, respectively). There was no significant difference in the levels of vascular inflammation markers between DADA2 patients with vasculitis and hematological involvement except IL-18. The plasma IL-18 levels were higher in the DADA2 patients with hema-tological findings compared to vasculitic phenotype (p=0.001). Finally DADA2 patients with neuropathy had higher sRAGE concentrations than patients without neuropathy and healthy controls (p=0.03 and p=0.008, respectively). Conclusion: We suggest that the high plasma IL-18 levels may be associated with an activated IFN pathway, the pathogenesis of hematologic manifestations, and unresponsive to anti-TNF treatment. Higher concentrations of Tie-1, Tie-2, sFlt-1, sRAGE, and TNF-α distinguished DADA2 patients with PAN-like features from PAN patients. We identified sRAGE as a potential biomarker of neuropathy in DADA2 patients. REFERENCES: [1] Pesciotta EN, Lam H-S, Kossenkov A, et al. In-Depth, Label-Free analysis of the erythrocyte cytoplasmic proteome in Diamond Blackfan Anemia identifies a unique inflammatory signature. PLoS One 2015;10(10):e0140036. [2] Haslbeck KM, Bierhaus A, Erwin S, et al. Receptor for advanced glycation endproduct (RAGE)-mediated nuclear factor-κB activation in vasculitic neu-ropathy. Muscle Nerve 2004;29(6):853-60. Background: Despite earlier diagnosis and improved management of rheumatic and musculoskeletal diseases (RMDs), a work participation gap remains when compared to the general population. To bridge this work participation gap, EULAR's current strategy states that 'by 2023, EULAR's activities and related advocacy will have increased participation in work by people with RMDs'. To achieve this goal, guidance is needed how to support people with RMDs to remain in paid work or (re)-enter the labour force. Objectives: To develop Points to Consider (PtC) when supporting people with RMD to participate in healthy and sustainable paid work. Methods: An international expert group, established by Eular in 2019, convened twice to agree on a protocol for the development of PtC. EULAR's standard operating procedures were followed. The group (a) defined the target audience, (b) identified areas from which knowledge should be derived to enable formulation of the PtC, (c) agreed on a strategy to collect evidence, (d) established an international taskforce to formulate and agree on the PtC, and (e) proposed an implementation plan.