Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives

Anaphylaxis is a type I hypersensitivity reaction that is potentially fatal if not promptly treated. It is a clinical diagnosis, although measurement of serial serum total mast cell tryptase (MCT) is gold standard and may help differentiate anaphylaxis from its mimics. The performance characteristic...

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Main Authors: Sarah C. Beck, Thomas Wilding, Richard J. Buka, Richard L. Baretto, Aarnoud P. Huissoon, Mamidipudi T. Krishna
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00494/full
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author Sarah C. Beck
Thomas Wilding
Richard J. Buka
Richard L. Baretto
Aarnoud P. Huissoon
Mamidipudi T. Krishna
Mamidipudi T. Krishna
author_facet Sarah C. Beck
Thomas Wilding
Richard J. Buka
Richard L. Baretto
Aarnoud P. Huissoon
Mamidipudi T. Krishna
Mamidipudi T. Krishna
author_sort Sarah C. Beck
collection DOAJ
description Anaphylaxis is a type I hypersensitivity reaction that is potentially fatal if not promptly treated. It is a clinical diagnosis, although measurement of serial serum total mast cell tryptase (MCT) is gold standard and may help differentiate anaphylaxis from its mimics. The performance characteristics of MCT assays in anaphylaxis has been variable in previous studies, due to multiple factors including differences in the definition of anaphylaxis, methods of MCT interpretation, clinical setting of anaphylaxis, causative agents, and timing of blood sample. An international consensus equation for MCT to interpret mast cell activation has been proposed and recently validated in the context of peri-operative anaphylaxis during general anesthesia. There has been an interest in the detection of newer biomarkers in anaphylaxis including platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, and CCL-2. The key determinants of an ideal biomarker in anaphylaxis are half-life, sample handling and processing requirements, and cost. There may be a role for metabolomics and systems biology in the exploration of novel biomarkers in anaphylaxis. Future studies applying these approaches might provide greater insight into factors determining severity, clinical risk stratification, identification of mast cell disorders and improving our understanding of this relatively complex acute immunological condition. Post mortem MCT evaluation is used in Forensic Medicine during autopsy for cases involving sudden death or suspected anaphylaxis. Interpretation of post mortem MCT is challenging since there is limited published evidence and the test is confounded by multiple variables largely linked to putrefaction and site of sampling. Thus, there is no international consensus on a reference range. In this state of the art review, we will focus on the practical challenges in the laboratory diagnosis of anaphylaxis and critically appraise (a) performance characteristics of MCT in anaphylaxis in different clinical scenarios (b) the role for novel biomarkers and (c) post mortem MCT and its role in fatal anaphylaxis.
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spelling doaj.art-2193910af43d4539b5cc84808619c9272022-12-21T18:41:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00494434681Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and PerspectivesSarah C. Beck0Thomas Wilding1Richard J. Buka2Richard L. Baretto3Aarnoud P. Huissoon4Mamidipudi T. Krishna5Mamidipudi T. Krishna6Department of Allergy and Immunology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomDepartment of Allergy and Immunology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomDepartment of Allergy and Immunology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomDepartment of Allergy and Immunology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomDepartment of Allergy and Immunology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomAnaphylaxis is a type I hypersensitivity reaction that is potentially fatal if not promptly treated. It is a clinical diagnosis, although measurement of serial serum total mast cell tryptase (MCT) is gold standard and may help differentiate anaphylaxis from its mimics. The performance characteristics of MCT assays in anaphylaxis has been variable in previous studies, due to multiple factors including differences in the definition of anaphylaxis, methods of MCT interpretation, clinical setting of anaphylaxis, causative agents, and timing of blood sample. An international consensus equation for MCT to interpret mast cell activation has been proposed and recently validated in the context of peri-operative anaphylaxis during general anesthesia. There has been an interest in the detection of newer biomarkers in anaphylaxis including platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, and CCL-2. The key determinants of an ideal biomarker in anaphylaxis are half-life, sample handling and processing requirements, and cost. There may be a role for metabolomics and systems biology in the exploration of novel biomarkers in anaphylaxis. Future studies applying these approaches might provide greater insight into factors determining severity, clinical risk stratification, identification of mast cell disorders and improving our understanding of this relatively complex acute immunological condition. Post mortem MCT evaluation is used in Forensic Medicine during autopsy for cases involving sudden death or suspected anaphylaxis. Interpretation of post mortem MCT is challenging since there is limited published evidence and the test is confounded by multiple variables largely linked to putrefaction and site of sampling. Thus, there is no international consensus on a reference range. In this state of the art review, we will focus on the practical challenges in the laboratory diagnosis of anaphylaxis and critically appraise (a) performance characteristics of MCT in anaphylaxis in different clinical scenarios (b) the role for novel biomarkers and (c) post mortem MCT and its role in fatal anaphylaxis.https://www.frontiersin.org/article/10.3389/fimmu.2019.00494/fullanaphylaxismast cellstryptasebiomarkersdiagnosis
spellingShingle Sarah C. Beck
Thomas Wilding
Richard J. Buka
Richard L. Baretto
Aarnoud P. Huissoon
Mamidipudi T. Krishna
Mamidipudi T. Krishna
Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives
Frontiers in Immunology
anaphylaxis
mast cells
tryptase
biomarkers
diagnosis
title Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives
title_full Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives
title_fullStr Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives
title_full_unstemmed Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives
title_short Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives
title_sort biomarkers in human anaphylaxis a critical appraisal of current evidence and perspectives
topic anaphylaxis
mast cells
tryptase
biomarkers
diagnosis
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00494/full
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AT aarnoudphuissoon biomarkersinhumananaphylaxisacriticalappraisalofcurrentevidenceandperspectives
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