The role of vascular inflammation markers in deficiency of adenosine deaminase 2.

OBJECTIVES

The first objective was to assess the role of vascular inflammatory factors in the pathogenesis of deficiency of adenosine deaminase 2 (DADA2) and to compare these markers among DADA2 patients with different phenotypes. We also aimed to investigate differences between DADA2 patients with vasculitic features and classic polyarteritis nodosa (PAN) for the aforementioned markers.

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. 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). In DADA2 patients with hematological findings, plasma IL-18 levels were higher than those with PAN-like 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).

CONCLUSIONS

We suggest that the high plasma IL-18 levels observed in DADA2 patients with hematologic manifestations may be associated with an activated IFNγ pathway, and lack of response to anti-TNF treatment. We identified sRAGE as a potential biomarker of neuropathy in DADA2 patients. Higher concentrations of Tie-1, Tie-2, sFlt-1, sRAGE, and TNF-α distinguished DADA2 patients with PAN-like features from PAN patients.