αIIb-Integrin (CD41) associated with blood eosinophils is a potential biomarker for disease activity in eosinophilic esophagitis

Johansson, Mats W.; McKernan, Elizabeth; Fichtinger, Paul S.; Angulo, Evelyn L.; Bagley, Jennifer L.; Lee, Kristine E.; Evans, Michael D.; Lomeli, Luis D.; Mosher, Deane F.; Cook, Shelly; Gaumnitz, Eric A.; Mathur, Sameer K.

doi:10.1016/j.jaci.2020.01.022

Cited by 15 publications

(38 citation statements)

References 9 publications

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“…These “activated” eosinophils within circulation are more prone to arrest on endothelial-expressed VCAM-1 [ 39 ], and correlate with decreased lung function in subjects with mild asthma [ 40 ]. A similar scenario of activation of eosinophil-expressed β1 integrins appears to occur in EoE patients [ 41 ] and may correlate with disease activity [ 42 ]. Moreover, reports of two case studies demonstrated a higher percentage of CD274 + (PDL1) blood eosinophils in EoE with reduction back down to normal levels following successful treatment [ 43 ].…”

Section: Eosinophil Heterogeneitymentioning

confidence: 91%

Heterogeneity of Intestinal Tissue Eosinophils: Potential Considerations for Next-Generation Eosinophil-Targeting Strategies

Masterson

Menard‐Katcher

Larsen

et al. 2021

Cells

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Eosinophils are implicated in the pathophysiology of a spectrum of eosinophil-associated diseases, including gastrointestinal eosinophilic diseases (EGIDs). Biologics that target the IL-5 pathway and are intended to ablate eosinophils have proved beneficial in severe eosinophilic asthma and may offer promise in treating some endotypes of EGIDs. However, destructive effector functions of eosinophils are only one side of the coin; eosinophils also play important roles in immune and tissue homeostasis. A growing body of data suggest tissue eosinophils represent a plastic and heterogeneous population of functional sub-phenotypes, shaped by environmental (systemic and local) pressures, which may differentially impact disease outcomes. This may be particularly relevant to the GI tract, wherein the highest density of eosinophils reside in the steady state, resident immune cells are exposed to an especially broad range of external and internal environmental pressures, and greater eosinophil longevity may uniquely enrich for co-expression of eosinophil sub-phenotypes. Here we review the growing evidence for functional sub-phenotypes of intestinal tissue eosinophils, with emphasis on the multifactorial pressures that shape and diversify eosinophil identity and potential targets to inform next-generation eosinophil-targeting strategies designed to restrain inflammatory eosinophil functions while sustaining homeostatic roles.

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Section: Eosinophil Heterogeneitymentioning

confidence: 91%

Heterogeneity of Intestinal Tissue Eosinophils: Potential Considerations for Next-Generation Eosinophil-Targeting Strategies

Masterson

Menard‐Katcher

Larsen

et al. 2021

Cells

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“…Nucleotide stimulation of human eosinophils was reported almost 30 years ago when it was shown that extracellular ATP secreted by thrombin-stimulated platelets exerted chemoattractant effects on human eosinophils (93,94). Of note, the interaction of platelets and eosinophils contributing to tissue inflammation and remodeling was demonstrated in later studies (95)(96)(97).…”

Section: Nucleotide Mediated Responses In Eosinophilsmentioning

confidence: 98%

Eosinophils and Purinergic Signaling in Health and Disease

et al. 2020

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Eosinophils are major effector cells against parasites, fungi, bacteria, and viruses. However, these cells also take part in local and systemic inflammation, which are central to eczema, atopy, rhinitis, asthma, and autoimmune diseases. A role for eosinophils has been also shown in vascular thrombotic disorders and in cancer. Many, if not all, above-mentioned conditions involve the release of intracellular nucleotides (ATP, ADP, UTP, etc.) and nucleosides (adenosine) in the extracellular environment. Simultaneously, eosinophils further release ATP, which in autocrine and paracrine manners, stimulates P2 receptors. Purinergic signaling in eosinophils mediates a variety of responses including CD11b induction, ROI production, release of granule contents and enzymes, as well as cytokines. Exposure to extracellular ATP also modulates the expression of endothelial adhesion molecules, thereby favoring eosinophil extravasation and accumulation. In addition, eosinophils express the immunosuppressive adenosine P1 receptors, which regulate degranulation and migration. However, pro-inflammatory responses induced by extracellular ATP predominate. Due to their important role in innate immunity and tissue damage, pharmacological targeting of nucleotide- and nucleoside-mediated signaling in eosinophils could represent a novel approach to alleviate eosinophilic acute and chronic inflammatory diseases. These innovative approaches might also have salutary effects, particularly in host defense against parasites and in cancer.

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“…There is an obvious need for biomarkers to replace such invasive and expensive monitoring. We recently demonstrated by flow cytometry that the percentage of blood eosinophils positive for CD41 (cluster of differentiation antigen 41, ITGA2B, α IIb subunit of the major platelet-specific integrin) correlated with peak eosinophil count (PEC) per microscopic high power field (HPF) of esophageal biopsies from EoE patients after standard of care treatment [ 3 ]. We screened for 16 possible eosinophil-surface markers and CD41 was the one that correlated best with and predicted PEC [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…We recently demonstrated by flow cytometry that the percentage of blood eosinophils positive for CD41 (cluster of differentiation antigen 41, ITGA2B, α IIb subunit of the major platelet-specific integrin) correlated with peak eosinophil count (PEC) per microscopic high power field (HPF) of esophageal biopsies from EoE patients after standard of care treatment [ 3 ]. We screened for 16 possible eosinophil-surface markers and CD41 was the one that correlated best with and predicted PEC [ 3 ]. Blood eosinophil CD41 positivity predicted after-treatment PEC < 6/HPF [ 3 ], a cutoff that has been used in various studies as a measure of remission of EoE [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…We screened for 16 possible eosinophil-surface markers and CD41 was the one that correlated best with and predicted PEC [ 3 ]. Blood eosinophil CD41 positivity predicted after-treatment PEC < 6/HPF [ 3 ], a cutoff that has been used in various studies as a measure of remission of EoE [ 4 , 5 ]. We suggested, therefore, that platelet-eosinophil complexes as measured by percentage CD41+ eosinophils may be a useful biomarker of EoE activity [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Platelet association with leukocytes in active eosinophilic esophagitis

et al. 2021

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We previously demonstrated that the percentage of blood eosinophils that are associated with platelets and thus positive for CD41 (integrin αIIb-subunit) correlates with and predicts peak eosinophil count (PEC) in biopsies of eosinophilic esophagitis (EoE) patients after treatment. Thus, flow cytometric determination of CD41+ eosinophils is a potential measure of EoE disease activity. Determinants of association of platelets with eosinophils and other leukocytes in EoE are largely unknown. The objectives of this study were to test the hypotheses that platelets associate with blood leukocytes other than eosinophils in EoE and that such associations also predict EoE activity. Whole blood flow cytometry was performed on samples from 25 subjects before and after two months of standard of care EoE treatment. CD41 positivity of cells within gates for eosinophils, neutrophils, monocytes, lymphocytes, and natural killer cells was compared. We found that percent CD41+ neutrophils, monocytes, and eosinophils correlated with one another such that principal component analysis of the five cell types identified “myeloid” and “lymphoid” factors. Percent CD41+ neutrophils or monocytes, or the myeloid factor, like CD41+ eosinophils, correlated with PEC after treatment, and CD41+ neutrophils or the myeloid factor predicted PEC < 6/high power field after treatment, albeit with lower area under the curve than for CD41+ eosinophils. We conclude that the processes driving platelets to associate with eosinophils in EoE also drive association of platelets with neutrophils and monocytes and that association of platelets with all three cell types is related to disease activity. Clinicaltrials.gov identifier: NCT02775045.

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αIIb-Integrin (CD41) associated with blood eosinophils is a potential biomarker for disease activity in eosinophilic esophagitis

Cited by 15 publications

References 9 publications

Heterogeneity of Intestinal Tissue Eosinophils: Potential Considerations for Next-Generation Eosinophil-Targeting Strategies

Heterogeneity of Intestinal Tissue Eosinophils: Potential Considerations for Next-Generation Eosinophil-Targeting Strategies

Eosinophils and Purinergic Signaling in Health and Disease

Platelet association with leukocytes in active eosinophilic esophagitis

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