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Abstract

To the Editor: Conus et al1Conus S. Straumann A. Simon H.-U. Anti–IL-5 (mepolizumab) therapy does not alter IL-5 receptor α levels in patients with eosinophilic esophagitis.J Allergy Clin Immunol. 2009; 123: 269Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar report that they did not observe increased levels of IL-5 receptor α (IL-5Rα) on eosinophils after anti–IL-5 therapy (mepolizumab) in a small cohort of patients with eosinophilic esophagitis. This observation is in contrast to our recent observations that anti–IL-5 therapy increases IL-5Rα levels on eosinophils, IL-5–circulating levels (caused by a long-lived mepolizumab/IL-5 complex), and production of IL-5 by circulating CD4 and CD8 cells.2Stein M.L. Villanueva J.M. Buckmeier B.K. Yamada Y. Filipovich A.H. Assa'ad A.H. et al.Anti–IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels.J Allergy Clin Immunol. 2008; 121: 1473-1483Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Our published results indeed have to be interpreted with caution given the small sample size (25 treated individuals), the lack of a placebo control group, and the heterogeneity of the patient population, which includes patients with diverse eosinophilic disorders, including eosinophilic esophagitis. Even more caution is warranted in the interpretation of the results of Conus et al.1Conus S. Straumann A. Simon H.-U. Anti–IL-5 (mepolizumab) therapy does not alter IL-5 receptor α levels in patients with eosinophilic esophagitis.J Allergy Clin Immunol. 2009; 123: 269Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar In particular, their sample size is notably small based on their prior abstract (5 patients given active drug and 6 patients given placebo)3Straumann A. Conus S. Kita H. Kephart G. Bussman C. Belgliner C. et al.Mepolizumab, a humanized monoclonal antibody to IL-5, for severe eosinophilic esophagitis in adults: a randomized placebo-controlled double-blind trial.J Allergy Clin Immunol. 2008; 121: S44Abstract Full Text Full Text PDF Google Scholar; even our results revealed only an 18% increase of IL-5Rα levels in a larger cohort. As such, the study by Conus et al1Conus S. Straumann A. Simon H.-U. Anti–IL-5 (mepolizumab) therapy does not alter IL-5 receptor α levels in patients with eosinophilic esophagitis.J Allergy Clin Immunol. 2009; 123: 269Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar is unlikely to be powered to find this difference. Furthermore, Conus et al do not provide reassurance that their mean fluorescence is calibrated so that it can be compared at different time points in clinical samples. Additionally, Conus et al used a different protocol than ours; they used an escalating dose of mepolizumab and different dosing intervals, whereas we used a fixed dose for 3 separate monthly infusions. Furthermore, Conus et al have misinterpreted our results concerning the inability of IL-5 to directly reduce IL-5Rα levels. In our study the experimental conditions were established to determine whether IL-5 and the anti–IL-5Rα antibody recognized the same epitope; by ruling out this possibility, we demonstrate that the detection of IL-5Rα after anti–IL-5 treatment in vivo was not influenced by the increased IL-5 levels in vivo. Additionally, our results are consistent with more elegant and controlled studies in mice, which have reported increased IL-5 levels in eosinophil-deficient mice,4Swartz J.M. Dyer K.D. Cheever A.W. Ramalingam T. Pesnicak L. Domachowske J.B. et al.Schistosoma mansoni infection in eosinophil lineage-ablated mice.Blood. 2006; 108: 2420-2427Crossref PubMed Scopus (153) Google Scholar supporting our proposal that an endogenous autoregulatory pathway (involving eosinophils) regulates IL-5 levels. Our results demonstrate reduced eosinophil levels in vivo and eosinophil activation ex vivo, providing supportive evidence for the clinical utility of anti–IL-5 therapy. The finding that this therapy increases IL-5Rα and IL-5 production has clinical significance; it urges cautious monitoring of patients as they are primed for recurrent eosinophilia when anti–IL-5 levels wane.