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

Abstract

Background Interleukin (IL)-5 plays a central role in the development and maintenance of eosinophilia and eosinophil activation in a wide variety of eosinophilic disorders. Although IL-5, IL-3 and GM-CSF can modulate 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 surface and soluble IL-5Rα levels in patients with eosinophilia and/or mastocytosis. Methods Surface IL-5Rα expression was assessed by flow cytometry in blood and/or bone marrow from subjects with eosinophilia (n=39), systemic mastocytosis (n=8) and normal volunteers (n=28). Soluble IL-5Rα (sIL-5Rα) was measured in a cohort of 177 untreated subjects and correlated with eosinophilia, eosinophil activation, serum tryptase and cytokine levels. Results Whereas IL-5Rα expression on eosinophils inversely correlated with eosinophilia (r=−0.48, p<0.0001), serum levels of sIL-5Rα increased with eosinophil count (r=0.56, p<0.0001), serum IL-5 (r=0.40, p<0.0001) and IL-13 levels (r=0.29, p=0.004). Of interest, sIL-5Rα was significantly elevated in patients with systemic mastocytosis without eosinophilia. 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 to normal subjects. Conclusion 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 surface and soluble receptor levels. This may have implications with respect to the use of novel therapeutic agents targeting IL-5 and its receptor in patients with eosinophilia and/or mastocytosis.

IL12Rβ1ΔTM Is a Secreted Product ofil12rb1That Promotes Control of Extrapulmonary Tuberculosis

“…The levels of spliced EPOR in the serum of dialysis patients correlates with the amount of therapeutic recombinant erythropoietin required by the same individuals (40). Bronchoalveolar lavage levels of spliced IL6R␣ are indicative of chronic lung disease in premature infants (55), while increased serum levels of spliced IL5R␣ are indicative of systemic abundance of mast cells (56). Pertaining to cancer, multiple myeloma patients have increased serum levels of spliced OSMR relative to healthy individuals (43), while an increased level of IL15R␣ in head and neck cancer patients is predictive of a poor clinical outcome (48).…”

Novel Therapies for Eosinophilic Disorders

“…117–119 Reliable biomarkers of disease activity, remission and drug responsiveness other than blood eosinophil counts would improve disease management, including confidence and safety during tapering of treatment. 120, 121 Examples of such biomarkers might include the presence of an activated eosinophil surface phenotype as detected by flow cytometry, 122, 123 , and a variety of measurements in biological fluids such as serum periostin in IL-13-driven asthma; 124, 125 serum CCL17 in HES and atopic dermatitits; 29, 126 serum levels of soluble receptors such as for IL-5, EMR1 and Siglec-8 in various forms of HES; 16, 121, 127 and detection of EPX in biological fluids. 128 Some studies suggest that elevated levels of IL-5 might be a feature of certain subsets of eosinophilic disorders 129, 130 as well as responsiveness to anti-IL-5 treatment.…”

Biologic Agents for the Treatment of Hypereosinophilic Syndromes

“…Moreover, benralizumab may be effective in M-HES where eosinophils may be IL-5-independent, but retain IL-5R on their surface. Potential disadvantages include the observation that in untreated patients, as AEC increases, IL-5Rα expression decreases and soluble IL-5Rα levels increase 35 . This could lead to decreased efficacy in patients with the highest AECs (i.e.…”