Monitoring eosinophils to guide therapy with biologics in asthma: does the compartment matter?

Abstract

Eosinophils, since their initial description by Thomas Wharton Jones in 1846, and staining characteristics by Paul Ehrlich in 1879, have been associated with asthma.1 They are produced in the bone marrow, from pluripotential stem cells, which first differentiate, largely regulated by a transcription factor GATA-1, into a hybrid precursor for both basophils and eosinophils, and then into a separate eosinophil lineage. The eosinophilopoietins IL-3, GM-CSF and notably IL-5 regulate their further expansion and migration out of the bone marrow, and into the circulation. Circulating eosinophils subsequently interact with the endothelium by processes involving rolling, adhesion and diapedesis. Depending on the target organ, eosinophils cross the endothelium into tissues by a regulated process involving the coordinated interaction between networks involving cytokines such as IL-13, the chemokine eotaxin-1, eosinophil adhesion molecules (α4β1, α4β7, αmβ2, αLβ2), and adhesion receptors on the endothelium (MAdCAM-1, VCAM-1 and ICAM-1). Under homeostatic conditions, eosinophils traffic into the thymus, mammary gland, uterus and most prominently into the gastrointestinal tract.2 Thus, in a disease such as asthma, long associated with mobilization of eosinophils from the bone marrow, it is not surprising that eosinophil numbers may be increased in blood and sputum in patients with asthma. The development of biologics targeting IL-5 and IL-13 has provided opportunities to treat patients with asthma whose severity or symptoms are driven by eosinophil biology. Most studies evaluating these biologics were conducted by selecting patients with raised blood eosinophil numbers, and not by enumerating numbers in the airway, as the latter process is cumbersome. There is ongoing controversy as to which would be a better strategy. This commentary examines whether blood eosinophil number is an adequate method to choose those patients who may be good responders to anti-eosinophil biologics and to monitor the response to therapy. Leo Koenderman and Marwan Hassani. Manali Mukherjee and Parameswaran Nair. Dr Nair was supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. Dr Mukherjee was supported by a Canadian Institutes of Health Research post-doctoral fellowship. The data in the manuscript was supported by a grant from the Canadian Institute of Health Research. LK reports grants from GlaxoSmithKline and non-financial support from Beckman Coulter. MH declares no conflicts of interests. MM reports grants from Methapharm Specialty Pharmaceuticals, Canadian Institute of Health Research, Canadian Asthma Allergy and Immunology Foundation and personal fees from AstraZeneca. PN reports grants and/or personal fees from AZ, Novartis, Teva, Sanofi, Roche, Novartis, Merck and Equillium.

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