Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid; Zotter, Zsuzsanna; Prohászka, Zoltán; Garred, Peter

doi:10.1016/j.jaci.2014.05.030

Cited by 15 publications

(11 citation statements)

References 28 publications

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“…Varga et al found that anti-C1-INH IgM antibody levels correlated with disease severity in C1-INH concentrate–naive patients [ 44 ]. Other reports indicated that the levels of Mannose-binding lectin-associated serine protease s (MASP-1, MASP-1)-C1-INH complexes are lower in C1-INH-HAE patients and correlate with the frequency of attacks [ 45 ], whereas the levels of MASP-2 and ficolin-3/MASP-2 complexes increase during attacks [ 46 ] (Table 1 ).…”

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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“… 45 , 46 It was explained that the lower MASP-2 levels were due to the consumption, and that the lectin pathway was still activated but depressed in HAE. 46 In one study, the concentrations of MASP-2 and ficolin-3/MASP-2 complex were increased during angioedema attacks compared with remission periods in the same HAE patient, 47 indicating that the lectin pathway was activated during attacks. Apart from its protease inhibitor role, C1–INH has many other biofunctions.…”

Section: Introductionmentioning

confidence: 97%

Does hereditary angioedema make COVID-19 worse?

Xu¹,

Liu²,

Zhi³

2020

World Allergy Organization Journal

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The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2) and depletes ACE2, which is necessary for bradykinin metabolism. The depletion of ACE2 results in the accumulation of des-Arg (9)-bradykinin and possible bradykinin, both of which bind to bradykinin receptors and induce vasodilation, lung injury, and inflammation. It is well known that an overactivated contact system and excessive production of bradykinin comprise the key mechanisms that drive the pathogenesis of hereditary angioedema (HAE). It is reasonable to speculate that COVID-19 may increase disease activity in patients with HAE and vice versa. In this review, we explore the potential interactions between COVID-19 and HAE in terms of the contact system, the complement system, cytokine release, increased T helper 17 cells, and hematologic abnormalities. We conclude with the hypothesis that comorbidity with HAE might favor COVID-19 progression and may worsen its outcomes, while COVID-19 might in turn aggravate pre-existing HAE and prompt the onset of HAE in asymptomatic carriers of HAE-related mutations. Based on the pathophysiologic links, we suggest that long-term prophylaxis should be considered in patients with HAE at risk of SARS-CoV-2 infection, especially the prophylactic use of C1 inhibitor and lanadelumab and that HAE patients must have medications for acute attacks of angioedema. Additionally, therapeutic strategies employed in HAE should be considered for the treatment of COVID-19, and clinical trials should be performed.

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“…Age‐ and gender‐matching of controls is often not considered necessary . At times, information concerning gender is even omitted , and in studies in which patient inclusion happens throughout the day and night the question of diurnal variation is not addressed .…”

Section: Introductionmentioning

confidence: 99%

Lectin complement pathway proteins in healthy individuals

Troldborg

Hansen

et al. 2017

Clinical and Experimental Immunology

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Since the discovery of the lectin pathway of complement activation, numerous clinical cohorts have been examined for one or more proteins, with the intention of uncovering the functions of the proteins or with the aim of discovering new biomarkers or diagnostic tools. To unveil the abnormal, it is pivotal to know the normal. Our aim was to describe the concentrations of the 11 known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigation in different cohorts. We examined the concentrations of all lectin pathway proteins mannan-binding lectin (MBL), H-ficolin, L-ficolin, M-ficolin, collectin-K1, collectin-L1, MBL-associated serine protease 2 (MASP-2), MASP-3, MBL-associated protein of 44 kDa (MAp44) and MAp19 in 300 Danish blood donors in serum and ethylenediamine tetraacetic acid (EDTA) plasma in established assays, and we further developed a new assay to measure MASP-1 in the same samples. We found significant differences in concentrations between serum and plasma for all proteins except for MBL and MASP-3. H-ficolin, M-ficolin and MAp19 displayed convincing diurnal variation. H-ficolin, in particular, halved from morning to the middle of the night. There were gender differences for most proteins, whereas age did not seem to influence concentration. The present study underlines the necessity of considering which material to use, correct matching and a trial design that takes the nature of the protein into account in order for the outcome of cohort studies to have significant relevance.

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Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

Cited by 15 publications

References 28 publications

Biomarkers in Hereditary Angioedema

Biomarkers in Hereditary Angioedema

Does hereditary angioedema make COVID-19 worse?

Lectin complement pathway proteins in healthy individuals

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