2D-LC–MS/MS to Measure Cleaved High-Molecular-Weight Kininogen in Human Plasma as A Biomarker for C1-Inh-Hae

Zhang, Guodong; Sexton, Daniel J.; Faucette, Ryan; Qiu, Yongchang; Wu, Jiang

doi:10.4155/bio-2017-0105

Cited by 18 publications

(6 citation statements)

References 48 publications

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“…Semi-quantification of results can be done by scanning gels [ 13 ]. New effective methods for cHK measurement are based on a monoclonal antibody ELISA [ 52 ] and modification of liquid chromatography–mass spectrometry [ 53 ]. Cugno et al observed, in patients with C1-INH-HAE, high levels of cHK during attacks and normal levels during remission [ 54 , 55 ].…”

Section: Biochemical Biomarkersmentioning

confidence: 99%

Biomarkers in Hereditary Angioedema

Porębski

Kwitniewski

Reshef

2021

Clinic Rev Allerg Immunol

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A biomarker is a defined characteristic measured as an indicator of normal, biologic, pathogenic processes, or biological responses to an exposure or intervention. Diagnostic biomarkers are used to detect a disease or a subtype of a disease; monitoring biomarkers are measured serially to assess a medical condition; response biomarkers are used to check biologic response following a medical intervention; predictive biomarkers are used to identify patients who are more likely to respond to a medical intervention; and prognostic biomarkers are used to assess the future likelihood of a clinical event. Although biomarkers have been extensively investigated and validated in many diseases and pathologies, very few are currently useful for the diagnosis, evaluation of disease activity, and treatment of hereditary angioedema (HAE). Pathophysiologic pathways involved in HAE reveal a plethora of molecules from the complement, coagulation, and fibrinolysis systems or from the vascular endothelium, which may serve as biomarkers. The most promising candidates, together with their laboratory readout systems, should be evaluated with regard to their analytical and clinical validity and utility. To be highly specific, such biomarkers should be linked to the pathomechanisms of HAE, particularly the bradykinin-generating cascade. Additionally, major advances in high-throughput omics-based technologies may facilitate the discovery of new candidate biomarkers in the future. This review will cover the existing as well as future potential biomarkers that will support the diagnosis, monitor disease activity, and can be used to assess the efficacy of new avenues of therapy of HAE and other forms of angioedema.

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Section: Biochemical Biomarkersmentioning

confidence: 99%

Biomarkers in Hereditary Angioedema

Porębski

Kwitniewski

Reshef

2021

Clinic Rev Allerg Immunol

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“…Another proposed approach to address bradykinin-mediated angioedema is the analysis of spontaneous amidase activity in plasma. The measurement of spontaneous amidase activity refers to the ability of different serine proteases, such as plasma kallikrein, factor XII, plasmin, and tissue plasminogen activator to hydrolyze specific synthetic peptides in vitro (usually HD-Pro-Phe-Arg-pNA or Z-Phe-Arg-AMC-HCl), and it is frequently used to evaluate the activation of the kallikrein-kinin system (65)(66)(67). Since most of the serine proteases circulate as zymogens in plasma, the activation of the proenzymes of the kallikreinkinin system can be achieved by the addition of negatively charged molecules such as dextran sulfate.…”

Section: Perspectives Of Tests For Bradykinin-mediated Angioedemamentioning

confidence: 99%

Angioedema Without Wheals: Challenges in Laboratorial Diagnosis

2021

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Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria. Recurrent angioedema without urticaria (AE) can be hereditary (HAE) and acquired (AAE), and several subtypes can be distinguished, although clinical presentation is quite similar in some of them. They present with subcutaneous and mucosal swellings, affecting extremities, face, genitals, bowels, and upper airways. AE is commonly misdiagnosed due to restricted access and availability of appropriate laboratorial tests. HAE with C1 inhibitor defect is associated with quantitative and/or functional deficiency. Although bradykinin-mediated disease results mainly from disturbance in the kallikrein–kinin system, traditionally complement evaluation has been used for diagnosis. Diagnosis is established by nephelometry, turbidimetry, or radial immunodiffusion for quantitative measurement of C1 inhibitor, and chromogenic assay or ELISA has been used for functional C1-INH analysis. Wrong handling of the samples can lead to misdiagnosis and, consequently, mistaken inappropriate approaches. Dried blood spot (DBS) tests have been used for decades in newborn screening for certain metabolic diseases, and there has been growing interest in their use for other congenital conditions. Recently, DBS is now proposed as an efficient tool to diagnose HAE with C1 inhibitor deficiency, and its use would improve the access to outbound areas and family members. Regarding HAE with normal C1 inhibitor, complement assays’ results are normal and the genetic sequencing of target genes, such as exon 9 of F12 and PLG, is the only available method. New methods to measure cleaved high-molecular-weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Validated biomarkers of kallikrein–kinin system activation could be helpful in differentiating mechanisms of angioedema. Our aim is to focus on the capability to differentiate histaminergic AE from bradykinin-mediated AE. In addition, we will describe the challenges developing specific tests like direct bradykinin measurements. The need for quality tests to improve the diagnosis is well represented by the variability of results in functional assays.

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“…This is mainly due to its wide availability for a reasonable price and its ability to cleave proteins into peptides of a size that is compatible with LC-MS/MS analysis on a triple quadrupole. If no suitable peptides are formed by trypsin, alternative enzymes such as chymotrypsin [5] or Glu-C [6] can also be used, or even chemical digestion, such as in the case of the presence of an acid-labile amide bond in the protein of interest [7].…”

Section: Digestionmentioning

confidence: 99%

Protein Quantification by LC–MS: A Decade of Progress Through the Pages of Bioanalysis

Merbel

2019

Bioanalysis

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Over the past 10 years, there has been a remarkable increase in the use of LC–MS for the quantitative determination of proteins, and this technique can now be considered an established bioanalytical platform for the quantification of macromolecular drugs and biomarkers, next to the traditional ligand-binding assays. Many researchers have contributed to the field and helped improve both the technical possibilities of LC–MS-based workflows and our understanding of the meaning of the results that are obtained. As a tribute to Bioanalysis, which has published many important contributions, this report gives a high-level overview of the most important trends in the field of protein LC–MS, as published in this journal since its inauguration a decade ago. It describes the major technical developments with regard to sample handling, separation and MS detection of both digested and intact protein analysis. In addition, the relevance of the complex structure and in vivo behavior of proteins is discussed and the effect of protein–protein interactions, biotransformation and the occurrence of isoforms on the analytical result is addressed.

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2D-LC–MS/MS to Measure Cleaved High-Molecular-Weight Kininogen in Human Plasma as A Biomarker for C1-Inh-Hae

Cited by 18 publications

References 48 publications

Biomarkers in Hereditary Angioedema

Biomarkers in Hereditary Angioedema

Angioedema Without Wheals: Challenges in Laboratorial Diagnosis

Protein Quantification by LC–MS: A Decade of Progress Through the Pages of Bioanalysis

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