Depressed activation of the lectin pathway of complement in hereditary angioedema

Varga, Lilian; Laki, Judit; Kocsis, Andrea; Kristóf, Katalin; Gál, Péter; Bajtay, Zsuzsa; Wieslander, Jörgen; Daha, Mohamed R.; Garred, Peter; Madsen, Hans O.; Füst, George; Farkas, Henriette

doi:10.1111/j.1365-2249.2008.03671.x

Cited by 16 publications

(11 citation statements)

References 32 publications

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“…However, compared with healthy controls, the activity of the MBL pathway and MASP-2 were found to be similar or even lower in HAE patients. 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.…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

Does hereditary angioedema make COVID-19 worse?

Xu¹,

Liu²,

Zhi³

2020

World Allergy Organization Journal

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“…Also relevant to our analysis, becasue of its participation in the complement activation pathway, is a potential role of mannose-binding lectin (MBL) in HAE pathogenesis. Recently, a strong correlation between MBL levels and activity of the lectin pathway was described in both HAE patients and healthy controls [19].…”

Section: Introductionmentioning

confidence: 99%

No Evidence for Linkage between the Hereditary Angiooedema Clinical Phenotype and the BDKR1, BDKR2, ACE or MBL2 gene

et al. 2011

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Hereditary angiooedema (HAE) is a life‐threatening disease with poor clinical phenotype correlation with its causal mutation in the C1 inhibitor (SERPING1) gene. It is characterized by substantial symptom variability even in affected members of the same family. Therefore, it is likely that genetic factors outside the SERPING1 gene have an influence on disease manifestation. In this study, functional polymorphisms in genes with a possible disease‐modifying effect, B1 and B2 bradykinin receptors (BDKR1, BDKR2), angiotensin‐converting enzyme (ACE) and mannose‐binding lectin (MBL2), were analysed in 36 unrelated HAE patients. The same analysis was carried out in 69 HAE patients regardless of their familial relationship. No significant influence of the studied polymorphisms in the BDKR1, BDKR2, ACE and MBL2 genes on overall disease severity, localization and severity of particular attacks, frequency of oedema episodes or age of disease onset was detected in either group of patients. Other genetic and/or environmental factors should be considered to be responsible for HAE clinical variability in Caucasians.

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“…The MASP-2 gene polymorphism exhibits a strong relationship with autoimmune diseases. Varga et al (2008) found that the lectin pathway might be activated in subjects with chlorine-esterase-inhibitor deficiency, which is associated with low MASP-2 and complement 4 levels. Thiel et al (2009) showed that human MASP-2 gene polymorphisms affect the protein folding of MASP-2 and binding efficiency of MASP-2 and mannan-binding lectin (MBL), in addition to autologous activation and serine protease activity.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms of the BMAP-28 and MASP-2 genes and their correlation with the somatic cell score in Chinese Holstein cattle

Jun¹,

Bai²,

Li³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. DNA sequencing, nested polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism were used to investigate mutations in the coding regions of the bovine myeloid antimicrobial peptide-28 (BMAP-28) and mannan-binding lectinassociated serine protease-2 (MASP-2) genes in 249 Chinese Holstein dairy cows. The associations between the polymorphisms and somatic cell score (SCS) were analyzed to determine the potential of these genes as genetic markers for breeding mastitis-resistant dairy cattle. The results revealed a C-86G synonymous mutation in the BMAP-28 gene that caused no alteration in the amino acid sequence. G553A mutation was found in the MASP-2 gene that led to the substitution of glycine with serine. The chi-square test showed that the G553A mutation was in Hardy-Weinberg equilibrium in the Chinese Holstein dairy cows, whereas the C-86G mutation was not. The variance analysis of the influence of group loci and different genotypes on the SCS showed that the SCS of genotype CC was significantly lower than those of genotypes CG and GG (P < 0.05) of the C-86G mutation, and that the SCS of genotype GG was significantly lower than those of genotypes GA and AA (P < 0.05) of the G553A mutation. Genotype combination analysis showed that the combination of the BMAP-28 genotype CC and the MASP-2 genotype GG was the best one, in which the SCS was significantly lower than those in the other combinations. Thus, this combination might be useful as a molecular and genetic marker of mastitis in Chinese Holstein dairy cows.

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Depressed activation of the lectin pathway of complement in hereditary angioedema

Cited by 16 publications

References 32 publications

Does hereditary angioedema make COVID-19 worse?

Does hereditary angioedema make COVID-19 worse?

No Evidence for Linkage between the Hereditary Angiooedema Clinical Phenotype and the BDKR1, BDKR2, ACE or MBL2 gene

Genetic polymorphisms of the BMAP-28 and MASP-2 genes and their correlation with the somatic cell score in Chinese Holstein cattle

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