Serum soluble Siglec-8 in hypereosinophilic syndromes

Abstract

Abstract Siglec-8, selectively expressed on eosinophils, basophils and mast cells, is the target of novel biologics in clinical development for eosinophil and mast cell-associated disorders. Since soluble Siglec-8 (sSiglec-8) can be detected in serum and could interfere with the efficacy of biologics targeting Siglec-8, the aim of the present study is to assess sSiglec-8 levels in a large cohort of subjects with hypereosinophilic syndrome (HES). sSiglec-8 levels were quantified in serum from normal (n=9) and eosinophilic (n=123) subjects using an in-house sandwich ELISA (limit of detection: 0.5 ng/mL) and correlated with Siglec-8 expression on the surface of eosinophils (measured by flow cytometry on whole blood eosinophils gated as granulocytes CD45+CD16neg) and absolute eosinophil count (AEC). The effects of treatment were also examined. Serum levels of sSiglec-8 were undetectable in 28 subjects, did not differ between untreated HES subjects and normal donors (GM 1.23 and 1.53 ng/mL), and did not correlate either with AEC (n=123) or with Siglec-8 surface expression on blood eosinophils (n= 35). There was also no clear relationship between the clinical subtype of HES and levels of sSiglec-8. Levels measured before and after varied HES treatments in 7 subjects showed a significant decrease from 1.82 to 0.50 ng/mL (P<0.05). In contrast, serum from 8 HES patients at two different time points on no treatment showed no significant change (GM 2.35 and 2.10 ng/mL respectively). These data suggest that, despite the lack of correlation with AEC, eosinophils are a significant source of sSiglec-8 in serum. Whether serum sSiglec-8 is predominantly from tissue eosinophils or mast cells, or requires eosinophil activation, is currently under investigation.