Pentraxin 3 level is elevated in hereditary hemorrhagic telangiectasia and reflects the severity of disease‐associated epistaxis

Steineger, Johan; Ueland, Thor; Aukrust, Pål; Michelsen, Anikka; Osnes, Terje; Heimdal, Ketil; Dheyauldeen, Sinan

doi:10.1002/lary.27548

Cited by 7 publications

(8 citation statements)

References 43 publications

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“…To evaluate the severity of the clinical presentation of the disease, clinicians are still searching for suitable biomarkers for HHT, which are missing in daily clinical use 41 – 43 . To that end, we correlated the results of HIF1A and HIF2A gene expression with the clinically determined Epistasis Severity Score of each individual HHT patient.…”

Section: Discussionmentioning

confidence: 99%

Altered hypoxia inducible factor regulation in hereditary haemorrhagic telangiectasia

Wrobeln

Leu

Jabłońska

et al. 2022

Sci Rep

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Patients with hereditary haemorrhagic telangiectasia (HHT), also known as Rendu–Osler–Weber syndrome, suffer from the consequences of abnormal vessel structures. These structures can lead to haemorrhages or shunt effects in liver, lungs and brain. This inherited and rare disease is characterized by mutations affecting the transforming growth factor-β (TGF-β)/Bone Morphogenetic Protein (BMP) pathway that results in arteriovenous malformations and studies indicate an impaired immune response. The mechanism underlying this altered immune response in HHT patients is still unknown. TGF-β interacts with hypoxia inducible factors (HIF), which both orchestrate inflammatory and angiogenic processes. Therefore, we analysed the expression of HIF and related genes in whole blood samples from HHT patients. We could show significantly decreased expression of HIF-1α on the mRNA and protein level. However, commonly known upstream regulators of HIF-1α in inflammatory responses were not affected, whereas HIF-1α target genes were significantly downregulated. There was no correlation between HIF1A or HIF2A gene expression and the severity of HHT detected. Our results represent a rare case of HIF-1α downregulation in a human disease, which underlines the relevance of HIFs in HHT. The study indicates an interaction of the known mutation in HHT and the dysregulation of HIF-1α in HHT patients, which might contribute to the clinical phenotype.

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Section: Discussionmentioning

confidence: 99%

Altered hypoxia inducible factor regulation in hereditary haemorrhagic telangiectasia

Wrobeln

Leu

Jabłońska

et al. 2022

Sci Rep

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“…Our current study failed to replicate these findings, which may be due to differences in anti-coagulant agents (EDTA vs. heparin) or due to the fact that our analysis did not stratify HHT patients based on genotype. Finally, one group found elevated levels of pentraxin 3 in plasma from HHT patients compared to healthy controls [ 15 ]. Interestingly, this marker was also more strongly associated with epistaxis-related scores than any other marker they assessed [ 15 ], supporting the hypothesis that there are indeed circulating biomarkers associated with disease-specific phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, one group found elevated levels of pentraxin 3 in plasma from HHT patients compared to healthy controls [ 15 ]. Interestingly, this marker was also more strongly associated with epistaxis-related scores than any other marker they assessed [ 15 ], supporting the hypothesis that there are indeed circulating biomarkers associated with disease-specific phenotypes. These studies, along with the data from our current study, highlight the need for further investigation into circulating factors that are associated with disease-specific phenotypes and events.…”

Section: Discussionmentioning

confidence: 99%

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations

Wetzel-Strong

Weinsheimer

Nelson

et al. 2021

Orphanet J Rare Dis

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Background Vascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifying patients at risk for complications or with certain disease phenotypes. Methods A validated multiplex protein array consisting of 26 angiogenic and inflammatory biomarkers (Angiome) was assessed in plasma isolated from healthy controls and patients with either sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformation (CCM), or hereditary hemorrhagic telangiectasia (HHT). These samples were obtained from archives of ongoing research studies at the University of California San Francisco and through prospective collection at the Toronto HHT Centre at St. Michael’s Hospital. Results We compared circulating biomarker levels from each patient group to healthy controls and analyzed each pairwise combination of patient groups for differences in biomarker levels. Additionally, we analyzed the HHT samples to determine the association between biomarker levels and the following HHT-specific phenotypes, BAVM, pulmonary arteriovenous malformation (PAVM), liver vascular malformation (LVM), and gastrointestinal (GI) bleeding. Compared to controls, levels of SDF1 were significantly elevated in HHT patients (Proportional Increase [PI] = 1.87, p < 0.001, q = 0.011). Levels of sENG were significantly reduced in HHT patients compared to controls (PI = 0.56, p < 0.001, q < 0.001), reflecting the prevalence of HHT1 patients in this cohort. Levels of IL6 (PI = 3.22, p < 0.001, q < 0.001) and sTGFβR3 (PI = 0.70, p = 0.001, q < 0.029) differed significantly in CCM patients compared to controls. Compared to controls, ten of the biomarkers were significantly different in sporadic BAVM patients (q-values < 0.05). Among the pairwise combinations of patient groups, a significant elevation was observed in TGFβ1 in CCM patients compared to sporadic BAVM patients (PI = 2.30, p < 0.001, q = 0.034). When examining the association of circulating biomarker levels with HHT-specific phenotypes, four markers were significantly lower in HHT patients with BAVM (q-values < 0.05), and four markers were significantly higher in patients with LVM (q-values < 0.05). Conclusions This pilot study suggests that the profile of circulating angiogenic and inflammatory biomarkers may be unique to each type of vascular malformation. Furthermore, this study indicates that circulating biomarkers may be useful for assessing phenotypic traits of vascular malformations.

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“…This database includes HHT patients, diagnosed clinically according to Curaçao criteria 3-4, and/or by additional genetic testing in the case of Curaçao 1-2. The patients included in this study were previously included in other studies concerning HHT-associated epistaxis (12)(13)(14)(15) and we collected IFT and ESS scores simultaneously. In these previous studies, the IFT and ESS scoring was performed either by the patients themselves or by the responsible doctor.…”

Section: Methodsmentioning

confidence: 99%

A comparative study of two grading systems for epistaxis in hereditary haemorrhagic telangiectasia

Jørgensen

Steineger

Bachmann-Harildstad

et al. 2021

Rhin

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BACKGROUND: Different institutions use different grading systems for hereditary haemorrhagic telangiectasia (HHT)-associated epistaxis. It is important to have a universal, standardized grading system to compare and evaluate the effectiveness of different treatment options. We introduced the “Intensity, Frequency and need for Blood Transfusion” (IFT) grading system for HHT-associated epistaxis in 2008. Hoag et al. proposed the “Epistaxis Severity Score” (ESS) for the International HHT foundation in 2010. This study aimed to evaluate the potential correlation between the ESS and IFT grading systems. METHODS: The study included 354 simultaneous reports using the IFT and ESS from 106 patients. The correlation between the ESS, IFT and haemoglobin levels was measured using Pearson’s correlation coefficient. The ESS and IFT were scored simultaneously by the patient and doctor in 48 cases to evaluate if there was a discrepancy in the scoring applied by either set of responders. RESULTS: The measured correlation between the two grading systems was good (0.75). The grade of epistaxis reported by patients and doctors respectively showed no significant difference. Both the IFT and ESS grading systems correlate significantly to the haemoglobin level. CONCLUSIONS: Both the IFT and ESS scores correlate to each other, and their results are comparable. Whether the IFT or ESS scoring was performed by the patient or doctor had no significant impact.

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Pentraxin 3 level is elevated in hereditary hemorrhagic telangiectasia and reflects the severity of disease‐associated epistaxis

Cited by 7 publications

References 43 publications

Altered hypoxia inducible factor regulation in hereditary haemorrhagic telangiectasia

Altered hypoxia inducible factor regulation in hereditary haemorrhagic telangiectasia

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations

A comparative study of two grading systems for epistaxis in hereditary haemorrhagic telangiectasia

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