OP0168 THE ROLE OF VASCULAR INFLAMMATION MARKERS IN DEFICIENCY OF ADENOSINE DEAMINASE 2

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 pathogenesis 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 neuropathy. 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 neurological 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 hematological 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.