Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease

Mitsui, Chihiro; Kondo, Keiichi; Hayashi, Hiroaki; Ito, Jun; Mita, Haruhisa; Ono, Emiko; Higashi, Noritaka; Fukutomi, Yuma; Sekiya, Kiyoshi; Tsuburai, Takahiro; Akiyama, Kazuo; Yamamoto, Kazuhiko; Taniguchi, Masami

doi:10.1016/j.jaci.2015.05.041

Cited by 60 publications

(63 citation statements)

References 48 publications

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“…Recently, novel mechanisms have been proposed, such as systemic inflammation, aberrant functions of platelets and overexpressed platelet activation242526. Aspirin challenge, for instance the ASA-BPT, is the gold standard for confirming aspirin hypersensitivity, however, there are still risks for bronchospasm as well as various contraindications27.…”

Section: Discussionmentioning

confidence: 99%

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Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Trinh

Kim

Cho

et al. 2016

Sci Rep

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Sphingolipid (SL) metabolites have been suggested to be important inflammatory mediators in airway inflammation and asthma. However, little is known about SL metabolites in aspirin-exacerbated respiratory disease (AERD). We aimed to explore the potential AERD biomarkers by conducting lipidomics targeting SL metabolites. The levels of SL metabolites in serum and urine samples from 45 AERD patients and 45 aspirin-tolerant asthma (ATA) patients were quantified through mass spectrometry. During the lysine-aspirin bronchoprovocation test (ASA-BPT), the levels of serum sphingomyelin (SM) were significantly decreased in AERD (P < 0.05) but not in ATA. The serum SM levels were positively correlated with airway responsiveness to methacholine. At the basal status before the ASA-BPT, the levels of serum sphingosine-1-phosphate (S1P) and urine sphingosine were significantly higher in the AERD patients compared with that of ATA patients (P < 0.001) and were positively correlated with a greater decrease in FEV1 (%) values following the ASA-BPT test (P < 0.001 for each), and with serum periostin level (P < 0.05 for each). This study is the first to evaluate serum S1P and urine sphingosine as potential biomarkers of AERD as well as to examine the metabolic disturbance of SL in AERD patients.

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Section: Discussionmentioning

confidence: 99%

“…Platelets contribute to the pathogenesis of AERD through various pathways, including the formation of platelet-leukocyte aggregates, abnormal function of platelets in vitro and overexpression of platelet activation252636. After platelet activation, intracellular S1P is released into the environment3738.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Trinh

Kim

Cho

et al. 2016

Sci Rep

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“…In addition, platelet MPs in plasma were reported to be significantly increased in subjects with asthma, which is one of the triad of conditions defining AERD 62 . Although growing evidence has suggested that abnormal platelet activation is uniquely associated with the pathophysiology of AERD independently of asthma 23, 24 further studies are necessary to clarify this point. However, PltMP levels in NLFs were higher in AERD than in CRSwNP with aspirin tolerant asthma, and the multivariate logistic analysis showed our cut-off values of platelet MPs, epithelial MPs, and mast cell MPs were significantly associated with AERD independently of asthma in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we found that some MP types, especially EpCAM+EpiMPs, PltMPs, and AV+MCMPs, are potential biomarkers for distinguishing AERD from CRSwNP in the clinic. Although platelet activation markers were reported to be potential diagnostic biomarkers for AERD in blood 23 , MP analysis in NLF may make diagnosis of AERD more robust by evaluating both EpiMPs and AV+MCMPs in addition to PltMPs. Recently, type 2 innate lymphoid cells have been detected in nasal polyp tissues and interest has focused on their role in the pathophysiology of CRS 64, 65 .…”

Section: Discussionmentioning

confidence: 99%

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Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease

Takahashi

Kato

Berdnikovs

et al. 2017

Journal of Allergy and Clinical Immunology

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Background Microparticles (MPs) are submicron sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been utilized as biomarkers to evaluate cell injury or activation in patients with pathological conditions. Objective To compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with NP (CRSwNP) and aspirin exacerbated respiratory disease (AERD). Methods We collected NLFs from CRSsNP (n=33), CRSwNP (n=45), AERD (n=31), and control (n=24) subjects. Standardized flow cytometry methods were used to characterize the following MP types; endothelial MPs, epithelial MPs (EpCAM(+)MPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EMR1(+)MPs), mast cell MPs (FcεRI(+)c-kit(+)MPs) and basophil MPs (CD203c(+)c-kit(−)MPs). Basophil activation was evaluated by the MFI of CD203c (CD203cMFI) on basophil MPs. Results Activated mast cell MPs (CD137(+)FcεRI(+)c-kit(+)MPs) were significantly increased in NLFs compared to controls in CRSsNP (2.3-fold, p<0.02), CRSwNP (2.3-fold, p<0.03) and in AERD (7.4-fold, p<0.0001). Platelet MPs (3.5-fold, p<0.01) and basophil MPs (2.5-fold, p<0.05) were increased only in AERD. CD203cMFI on MPs was increased in CRSwNP (p<0.002) and AERD (p<0.0001), but not CRSsNP. EpCAM(+)epithelial MPs in CRSwNP were no different from control (p= 0.91) and lower than those in CRSsNP (p<0.02) and AERD (p<0.002). Conclusion Based on released MPs, mast cells, platelets, and basophils were more highly activated in AERD than in CRS. Epithelial injury was lower in CRSwNP than in CRSsNP and AERD. MP analysis may help identify phenotypes of CRS, and in distinguishing AERD from CRSwNP.

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Immunology and Nanotechnology: Effects and Affects

Banerjee

Madhyastha

2021

Nanotechnology in the Life Sciences

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Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease

Cited by 60 publications

References 48 publications

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease

Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease

Immunology and Nanotechnology: Effects and Affects

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