γ' Fibrinogen as a Predictor of Survival in Amyotrophic Lateral Sclerosis

Pronto-Laborinho, Ana Catarina; Lopes, Catarina S.; Conceição, Vasco A.; Gromicho, Marta; Santos, Nuno C.; Carvalho, Mamede de; Carvalho, Filomena A.

doi:10.3389/fcvm.2021.715842

Cited by 4 publications

(5 citation statements)

References 20 publications

(35 reference statements)

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“…No other independent variable showed significant association with survival. The average survival in our ALS population was similar to other ALS studies 48,49 …”

Section: Resultssupporting

confidence: 89%

Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

Lopes,

Pronto‐Laborinho,

Conceição

et al. 2023

BioFactors

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Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS‐R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS‐R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS‐R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS‐R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.

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“…No other independent variable showed significant association with survival. The average survival in our ALS population was similar to other ALS studies 48,49 …”

Section: Resultssupporting

confidence: 89%

Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

Lopes,

Pronto‐Laborinho,

Conceição

et al. 2023

BioFactors

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“…Other studies have shown a positive correlation between the concentration of FIBB and survival in ALS patients [ 39 ]. Specifically, ALS patients who had higher levels of FIBB in their plasma exhibited longer survival periods, a finding consistent across various potential influencing factors like age, gender, respiratory issues, or functional ability [ 40 ]. C9 is among the proteins engaged in the complement system, serving as a defense mechanism of the body against pathogens [ 41 ].…”

Section: Discussionmentioning

confidence: 88%

Shotgun Proteomics Links Proteoglycan-4+ Extracellular Vesicles to Cognitive Protection in Amyotrophic Lateral Sclerosis

Vilardo,

De Marchi,

Raineri

et al. 2024

Biomolecules

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder lacking reliable biomarkers for early diagnosis and disease progression monitoring. This study aimed to identify the novel biomarkers in plasmatic extracellular vesicles (EVs) isolated from ALS patients and healthy controls (HCs). A total of 61 ALS patients and 30 age-matched HCs were enrolled in the study and the protein content of circulating EVs was analyzed by shotgun proteomics. The study was divided into a discovery phase (involving 12 ALS and 12 HC patients) and a validation one (involving 49 ALS and 20 HC patients). In the discovery phase, more than 300 proteins were identified, with 32 proteins showing differential regulation in ALS patients compared to HCs. In the validation phase, over 400 proteins were identified, with 20 demonstrating differential regulation in ALS patients compared to HCs. Notably, seven proteins were found to be common to both phases, all of which were significantly upregulated in EVs from ALS patients. Most of them have previously been linked to ALS since they have been detected in the serum or cerebrospinal fluid of ALS patients. Among them, proteoglycan (PRG)-4, also known as lubricin, was of particular interest since it was significantly increased in ALS patients with normal cognitive and motor functions. This study highlights the significance of EVs as a promising avenue for biomarker discovery in ALS. Moreover, it sheds light on the unexpected role of PRG-4 in relation to cognitive status in ALS patients.

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“…Studies have reported thinner fibers and a more branched network in clots made with γA/γ' fibrinogen compared to clots prepared from γA/γA fibrinogen [19][20][21] . γ' fibrinogen levels can vary largely between individuals and are associated with various diseases [22][23][24][25][26][27] .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…[19][20][21] γˊfibrinogen levels can vary largely between individuals and are associated with various diseases. [22][23][24][25][26][27] Since fibrinogen variants were previously associated with various thrombotic diseases and an altered fibrin network structure, we hypothesized that these fibrinogen variants would be increased in patients with severe COVID-19 and thrombosis. Therefore, we investigated whether levels of functional fibrinogen, total fibrinogen, intact fibrinogen, γf brinogen, and α E fibrinogen are altered in COVID-19 and whether this can explain why some patients with COVID-19 develop thrombosis and others do not.…”

Section: Introductionmentioning

confidence: 99%

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Levels of Fibrinogen Variants Are Altered in Severe COVID-19

de Vries,

Visser,

van Ommen

et al. 2023

TH Open

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Background: Fibrinogen variants as a result of alternative mRNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during COVID-19, potentially affecting disease severity or the thrombosis risk. Aim: To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods: In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. ELISAs were used to measure antigen levels of total, intact (non-degraded Aα chain), extended Aα chain (αE) and γ’ fibrinogen in health controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results: Healthy controls and ward patients with COVID-19 (n=10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did (n=19) or did not develop thrombosis (n=18) and ICU patients with pneumococcal infection (n=6) had higher absolute levels of functional, total, intact and αE fibrinogen than healthy controls (n=7). The relative αE fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ’ fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion: Our results show that severe COVID-19 is associated with increased levels of αE fibrinogen and decreased relative levels of γ’ fibrinogen, which may be cause or consequence of severe disease, but are not associated with the development of thrombosis.

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γ' Fibrinogen as a Predictor of Survival in Amyotrophic Lateral Sclerosis

Cited by 4 publications

References 20 publications

Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

Shotgun Proteomics Links Proteoglycan-4+ Extracellular Vesicles to Cognitive Protection in Amyotrophic Lateral Sclerosis

Levels of Fibrinogen Variants Are Altered in Severe COVID-19

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