IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis

Abstract

Background: IL-5 plays a central role in the development and maintenance of eosinophilia (EO) and eosinophil activation in a wide variety of eosinophilic disorders. Although IL-5, IL-3, and GM-CSF can modulate the expression of IL-5 receptor α (IL-5Rα) on eosinophils in vitro, little is known about soluble and surface IL-5Rα levels in vivo.

Objective: To assess soluble and surface IL-5Rα levels in patients with EO and/or mastocytosis.

Methods: Surface IL-5Rα expression was assessed by flow cytometry in blood and/or bone marrow from subjects with EO (n = 39) and systemic mastocytosis (n = 8) and from normal volunteers (n = 28). Soluble IL-5Rα (sIL-5Rα) level was measured in a cohort of 177 untreated subjects and correlated with EO, eosinophil activation, and serum tryptase and cytokine levels.

Results: IL-5Rα expression on eosinophils inversely correlated with EO (r = -0.48; P < .0001), whereas serum levels of sIL-5Rα increased with the eosinophil count (r = 0.56; P < .0001) and serum IL-5 (r = 0.40; P < .0001) and IL-13 (r = 0.29; P = .004) levels. Of interest, sIL-5Rα level was significantly elevated in patients with systemic mastocytosis without EO. Although sIL-5Rα levels correlated with serum tryptase levels in these patients, eosinophil activation, assessed by CD69 expression on eosinophils and serum eosinophil-derived neurotoxin levels, was increased compared with that in normal subjects.

Conclusions: These data are consistent with an in vivo IL-5Rα regulatory pathway in human eosinophils similar to that described in vitro and involving a balance between soluble and surface receptor levels. This may have implications with respect to the use of novel therapeutic agents targeting IL-5 and its receptor in patients with EO and/or mastocytosis.

Figure 1

Serum levels of sIL-5Rα are positively correlated with peripheral blood eosinophilia. Each circle represents an individual data point. Subjects with eosinophilic disease are shown in red, those with mastocytosis in blue and normals in green. The dotted line represents the limit of detection of the assay. P<0.0001, r = 0.54, Spearman rank correlation

Figure 2

Serum IL-5Rα levels are increased in patients with eosinophilia and mastocytosis without eosinophilia. Each symbol represents an individual data point. Subjects with eosinophilia are indicated in red, with mastocytosis in blue and normal controls in green. Group geometric means are indicated by horizontal lines. * p<0.001 or + p<0.05 compared to normal group (Holm’s adjusted p-value using the Mann-Whitney-U test)

Figure 3

Surface expression of IL-5Rα on eosinophils is inversely correlated with peripheral blood eosinophilia. Each circle represents an individual data point. Subjects with eosinophilic disease are shown in red, those with mastocytosis in blue and normals in green. ABC = antibodies bound per cell. P<0.0001, r = −0.48, Spearman rank correlation

Figure 4

Serum levels of sIL-5Rα are correlated with serum tryptase levels in patients with SM, but not HES without SM. Serum tryptase and sIL-5Rα levels are shown for subjects with SM (r=0.62, P<0.0001, Spearman rank correlation, panel A) and eosinophilia without SM (r=0.19, P=0.2, panel B). Each circle represents an individual data point.