Studies show that Angiopoietin-2 is a strong predictor in COVID-19 patients

Two research teams find that increased levels of the proinflammatory cytokine Angiopoietin-2 predicts transfer to the ICU and is responsible for hypercoagulation observed in critically ill COVID-patients.

Studies:

Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Smadja DM et al., Angiogenesis, 2020;1-10. Full text

Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients. Hultstrom M et al., MedRxiv preprint server, 2021. Full text

Click here for a summary of the findings.

Background

SARS-CoV-2 is the causative agent of the coronavirus respiratory disease COVID-19. It has a diverse range of symptoms and may cause severe illness, in particular in patients with cardiovascular risk factors (1).

Endothelial damage and inflammation in SARS-CoV-2 infection

The inflammatory cytokine storm occurring in COVID-19 patients, leads to the recruitment of leukocytes which damage the capillary endothelium. The endothelial damage and inflammation in several organs in SARS-CoV-2 infection is a direct consequence of viral involvement and of the host inflammatory response (2).
Despite the routine thrombosis prophylaxis as standard of care treatment, the major COVID-19 complication is the hyperactivation of the coagulation system indicating a poor prognosis among COVID-19 patients in intensive care (3).

Angiopoietin-2 (ANG2) is a soluble marker of endothelial activation

Angiopoietin-2 is an angiogenesis regulator that can be rapidly released by the activated endothelium upon thrombin or inflammatory cytokines. ANG2 induces inflammation and vascular hyperpermeability and correlates with adverse outcomes in several critical care syndromes (4, 5).

Angiopoietin-2 is a crucial factor to predict transfer to the ICU

In COVID-19 patients, ANG2 was recently reported by Smadja and colleagues to be a relevant factor to predict transfer to the ICU as it was associated with poor lung compliance (6). Thus, showing that endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.

Angiopoietin-2 inhibits anticoagulation in critically ill COVID-19 patients

Hulstrom and colleagues recently demonstrated that ANG2 levels in critically ill COVID-19 patients correlate with disease severity, hypercoagulation, and mortality. In addition, the researchers provided novel in vivo evidence for a direct role for ANG2 in coagulation through binding to and inhibition of thrombomodulin-mediated anticoagulation. The scientists suggest that inhibition of ANG2 might be beneficial for treating critically ill COVID-19 patients, as well as other patients with hypercoagulation (7).

About the Angiopoietin ELISA

  • Low sample volume – only 10µl needed
  • Assay range optimized for clinical samples
  • Ready to use standards and 2 controls included
  • Highly specific epitope mapped capture and detection antibodies

The human Angiopoietin-2 ELISA kit was developed and manufactured by Biomedica

Literature

  1. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Zhou F et al., Lancet, 2020; 395(10229):1054-1062.
  2. Endotheliitis in COVID-19. Varga S. Der Pathologe, 2020; 41(Suppl 2):99-102.
  3. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Al-Samkari H et al., Blood, 2020:136, 489-500.
    Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology. Akwii RG et al., Cells, 2019; 8(5): 471.
  4. Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies. Li F et al., Therapeutic advances in respiratory disease, 2020; 14, 1753466620905274.
  5. Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Smadja DM et al., Angiogenesis, 2020;1-10.
  6. Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients. Hultstrom M et al., MedRxiv preprint server, 2021.

Sclerostin expression in trabecular bone is down-regulated by osteoclasts

Scientific Reports

Bone tissues have trabecular bone with a high bone turnover rate and cortical bone with a low turnover. Expression of sclerostin by osteocytes works to inhibit bone formation. A study performed recently aimed to evaluate the relationship between the secretion of sclerostin by osteocytes and the secretion of leukemia inhibitory factor (LIF) by osteoclasts. It was found that LIF secretion effectively suppresses sclerostin expression and promotes bone formation.

Read the full article here.


Eagle Biosciences offers a sensitive and reliable assay for the detection of sclerostin in serum and plasma samples:

Sclerostin ELISA Assay Kit

Mouse LIF ELISA Assay Kit

Human LIFR ELISA Assay Kit

Free Soluble RANKL ELISA Assay Kit

If you are looking for any other specific Bone Monitoring related products or if you have questions about our offerings, contact us here.

EagleBio Endocrinology

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

Frontiers in Immunology

Numerous ELISA Assay Kits from our endocrinology line were used in a recent study published out of the University of Nebraska Medical Center in Omaha, Nebraska. These kits were used to analyze blood plasma for biomarkers that could implicate environmental triggers for the pathogenesis of Type 1 Diabetes. These kits included;

Anti-GAD ELISA Assay Kit

ICA screen ELISA Assay Kit

Anti-ZnT8 ELISA Assay Kit

Anti-IA2 ELISA Assay Kit

Anti-tTG IgA ELISA Assay Kit

High Sensitive Anti-TPO ELISA Assay Kit

Abstract


Multiple environmental triggers have been proposed to explain the increased incidence of type 1 diabetes (T1D). These include viral infections, microbiome disturbances, metabolic disorders, and vitamin D deficiency. Here, we used ELISA to examine blood plasma from juvenile T1D subjects and age-matched controls for the abundance of several circulating factors relevant to these hypotheses. We screened plasma for sCD14, mannose binding lectin (MBL), lipopolysaccharide binding protein (LBP), c-reactive protein (CRP), fatty acid binding protein 2 (FABP2), human growth hormone, leptin, total adiponectin, high molecular weight (HMW) adiponectin, total IgG, total IgA, total IgM, endotoxin core antibodies (EndoCAbs), 25(OH) vitamin D, vitamin D binding protein, IL-7, IL-10, IFN-γ, TNF-α, IL-17A, IL-18, and IL-18BPa. Subjects also were tested for prevalence of antibodies targeting adenovirus, parainfluenza 1/2/3, Coxsackievirus, cytomegalovirus, Epstein-Barr virus viral capsid antigen (EBV VCA), herpes simplex virus 1, and Saccharomyces cerevisiae. Finally, all subjects were screened for presence and abundance of autoantibodies targeting islet cell cytoplasmic proteins (ICA), glutamate decarboxylase 2 (GAD65), zinc transporter 8 (ZNT8), insulinoma antigen 2 (IA-2), tissue transglutaminase, and thyroid peroxidase, while β cell function was gauged by measuring c-peptide levels. We observed few differences between control and T1D subjects. Of these, we found elevated sCD14, IL-18BPa, and FABP2, and reduced total IgM. Female T1D subjects were notably elevated in CRP levels compared to control, while males were similar. T1D subjects also had significantly lower prevalence of EBV VCA antibodies compared to control. Lastly, we observed that c-peptide levels were significantly correlated with leptin levels among controls, but this relationship was not significant among T1D subjects. Alternatively, adiponectin levels were significantly correlated with c-peptide levels among T1D subjects, while controls showed no relationship between these two factors. Among T1D subjects, the highest c-peptide levels were associated with the lowest adiponectin levels, an indication of insulin resistance. In total, from our examination we found limited data that strongly support any of the hypotheses investigated. Rather, we observed an indication of unexplained monocyte/macrophage activation in T1D subjects judging from elevated levels of sCD14 and IL-18BPa. These observations were partnered with unique associations between adipokines and c-peptide levels among T1D subjects.

To learn more and read the full publication, click here.

For a full list of Eagle Bioscience’s Endocrinology line of ELISA kits click here.

Biomarker of urinary 5-HIAA as a valuable predictor of acute appendicitis

Science Direct

Acute appendicitis is one of the most common causes of severe acute abdominal pain globally. Increased levels of 5-Hydroxyindole acetic acid (5-HIAA), a metabolite of serotonin, in urine has been associated with acute appendicitis due to the densely packed serotonin-containing cells in the appendix. A study performed recently aimed to evaluate and determine the significance of 5-HIAA as a diagnostic marker.

Read the full article here.


Eagle Biosciences offers a sensitive and reliable assay for the detection of 5-HIAA in urine samples:

5-HIAA ELISA Assay Kit

Serotonin ELISA Assay Kit

Serotonin Ultrasensitive ELISA Assay Kit

If you are looking for any other specific 5-HIAA related product or if you have questions about our offerings, contact us here.

Eagle Biosciences Functional Leptin ELISA Assay Kit was utilized in a clinical study to monitor those with functional leptin deficiency. Circulating leptin levels in the body are crucial for maintaining body weight. This clinical study was developed to test for a valid diagnostic tool to detect functionally leptin in those who have defective leptin receptor binding. To view more information about our Leptin ELISA Assay Kit click here.

Abstract:

Context and aims: Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency.

Methods: An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep). The analytical quality of bioLep was validated and compared to a conventional assay for immune-reactive leptin (irLep). Its clinical relevance was evaluated in a cohort of lean and obese children and adults as well as in children diagnosed with functional leptin deficiency and their parents.

Results: In the clinical cohort, a bioLep/irLep ratio of 1.07 (range: 0.80–1.41) was observed. Serum of patients with non-functional leptin due to homozygous amino acid exchanges (D100Y or N103K) revealed high irLep but non-detectable bioLep levels. Upon treatment of these patients with metreleptin, irLep levels decreased, whereas levels of bioLep increased continuously. In patient relatives with heterozygous amino acid exchanges, a bioLep/irLep ratio of 0.52 (range: 0.48–0.55) being distinct from normal was observed.

Conclusions: The new bioLep assay is able to diagnose impaired leptin bioactivity in severely obese patients with a homozygous gene defect and in heterozygous carriers of such mutations. The assay serves as a diagnostic tool to monitor leptin bioactivity during treatment of these patients.

Wabitsch, M., Pridzun, L., Ranke, M., Schnurbein, J. V., Moss, A., Brandt, S., . . . Kratzsch, J. (2017). Measurement of immunofunctional leptin to detect and monitor patients with functional leptin deficiency. European Journal of Endocrinology,176(3), 315-322. doi:10.1530/eje-16-0821

FGF-23 is a hormone that is secreted by osteoblasts within the bones. This protein works with the kidneys to help regulated levels of phosphate in the blood/serum. The kidney gets rid of excess phosphate by excreting it in urine. When more phosphate is needed, the kidney reabsorb phosphate into the bloodstream. FGF-23 signals the kidneys to stop reabsorbing phosphate into the bloodstream. This fibroblastic growth factor binds to a receptor protein called FGF receptor 1. These receptors span the membrane of kidney cells. The binding of the protein and the receptors stimulates a signal cascade that stops phosphate reabsorption into the bloodstream.


image credit: https://www.kidney-international.org/

Why measure FGF-23?

Phosphate plays a critical role in the formation and growth of bones in children and for maintaining bone strength in adults. An imbalance in levels of FGF-23 in the body causes high or low levels of phosphate in the bloodstream. Low levels of phosphate in the blood can result in hypophosphatemia rickets or osteomalacia, which is a weakening of the bone which can cause bone pain and fractures. High levels of phosphate in the blood can indicate kidney disfunction.

Check out our two kits used for measuring FGF-23:

 

Mesothelioma is a malignant lung cancer that is commonly associated with previous asbestos exposure. Often it is not diagnosed until too late to treat in a patient. Calretinin has recently been in the spotlight as a potential biomarker for early detection of mesothelioma.

Two recent studies used Eagle Bioscience’s Calretinin ELISA Assay kit analyzing the accuracy of using Calretinin as a prediagnostic technique for mesothelioma:

  • Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.
    Aguilar-Madrid, Guadalupe, et al. “Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population .” International Journal of Medical Sciences, vol. 15, no. 9, 2018, pp. 883–891.
  • Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers.
    Johnen, G., Burek, K., Raiko, I., Wichert, K., Pesch, B., Weber, D. G., . . . Brüning, T. (2018). Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers. Scientific Reports,8(1).

Learn more about our Calretinin ELISA Assay kit here.