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By Dajana Domik
Neopterin is a broad range inflammation marker which can be measured in the blood of patients and indicates a multitude of diseases from acute viral infections to autoimmune conditions.1 This marker can serve as an essential “catch all” as neopterin levels are elevated due to any viral or bacterial invasion, which indicates an infection within the body without the need of several specific tests to confirm. This is an essential factor to keep patients safe in every situation from blood transfusions to COVID-19 critical care.
Neopterin can provide vital information on the progression of COVID-19.
Checking for specific diseases has its place. If a patient is suspected of being infected with a specific pathogen, then a specific test can be performed. However, when treating patients or handling patient material that needs to be examined for a broad range of infections raises some significant challenges. To know that a blood or urine sample is free from pathogens could require a barrage of expensive tests, assuming of course that a specific test exists and is commercially available. This approach means that diseases that do not yet have a viable diagnostic test cannot be tested for and can therefore slip through the net. Neopterin helps us understand what is going on and provides a head start for more specific tests. Let’s consider how it can be used as a universal inflammation marker in blood tests.
Why using neopterin is a no-brainer
Monitoring with a global disease marker is about mitigating the risk for patients. Neopterin can be applied as a universal marker for any pathogen invasion triggering its release by macrophages. Here the advantage is that one test hints at a range of diseases or disorders even if there is no specific test available. This is extremely useful in cases such as blood transfusions, where often a series of costly screening tests is necessary to rule out a specific disease.
Carrying out many different tests increases the time, cost and labor involved in administering blood transfusions which can ultimately mean that people do not get transfusions when they need them. It also means that diseases that are not specifically tested for can go undetected. Therefore, it makes sense to use a global marker such as neopterin. In fact, in Austria, a neopterin screen on all blood donations destined for transfusion is mandatory.2 However, if this is not the case in the rest of the world, perhaps it should be?
A global marker like neopterin could replace many of the tests that are carried out today in cases such as blood transfusions. However, even if they do not ultimately replace these other tests in practice, it makes sense to include a global “catch all” inflammation marker as a safety net.
What about other global disease markers?
While other global markers like C-reactive protein (CRP) exist, neopterin has the advantage that it is better suited to distinguish between viral and bacterial infections. This is especially crucial if the administration of antibiotics is in question. As discussed previously, neopterin is produced by macrophages in response to stimulation by interferon-γ. Neopterin can be produced locally but quickly spread systemically if the activation is high enough. CRP is activated by increasing levels of IL-6 which is also produced by macrophages.
However, CRP3 is produced in the liver and is quickly spread via the blood stream. One of the functions of CRP is to bind to invading microorganisms and activate the complement cascade. Both neopterin and CRP are produced in response to a wide range of diseases, from infections to autoimmune diseases and malignancies.
While both CRP and neopterin are global markers of various diseases, neopterin is especially suited for differentiating between viral and bacterial infections of the lower respiratory tract. This makes it a particularly important indicator for respiratory infections such as COVID-19.
Significance of neopterin for COVID-19 detection
When it comes to COVID-19, most people are aware of several common and specific clinical tests. However, neopterin is more frequently mentioned in relation to COVID-19 and a recent publication4 addressed how the severity and course of the disease correlates with neopterin.
Increasingly, neopterin remains a useful prognostic marker for COVID-19 for several reasons:
1. Neopterin levels increase before clinical symptoms manifest themselves and before antibodies can be detected. This can be incredibly useful to monitor high-risk populations who are more likely to require clinical intervention if they contract COVID-19.
2. Neopterin levels are elevated during COVID-19 infections. Therefore, individuals should be tested for neopterin levels during an COVID-19 infection.
3. Neopterin levels are correlated to the course and the severity of COVID-19. Therefore, suitable treatment and clinical interventions can be applied by healthcare professionals.
4. Neopterin levels allow for more effective triage of COVID-19 patients entering clinical-care facilities. It also means that resources in healthcare facilities can be allocated more effectively, saving resources for the most severe cases which can be predicted using neopterin measurement.
The successful treatment of COVID-19 relies on the management of symptoms that can become severe and ultimately lead to death. A lack of information early in the pandemic meant that effective triage of COVID-19 patients was not possible, and treatment could not be prioritized. This led to more severe cases of COVID-19 and avoidable fatalities.
Now we have a much better understanding of how the disease progresses and how to treat people so that even the most severe symptoms can be managed effectively if they are caught in time. Measurement of neopterin provides clinical staff with more information at an earlier stage, which ultimately improves the quality of care delivered to patients, can prevent severe illness, and could save lives. For more information, download our flyer: Interrogate COVID-19 with Tecan’s Neopterin ELISA.
References:
1. Hamerlinck, F. F. V. (1999). Neopterin: a review. Experimental dermatology, 8(3), 167-176.
2 Schennach, H., Mayersbach, P., Schönitzer, D., Fuchs, D., Wachter, H., & Reibnegger, G. Itzer,D., Fuchs, D., Wachter, H., & Reibnegger, G. (1994). Increased Prevalence of IgM Antibodies to Epstein-Barr Virus and Parvovirus B19 in Blood Donations with above-Normal Neopterin. Clin. Chem. 1994, 40 (11), 2104–2105.
3. Jain, S. et. al. (2011). Acute-phase proteins: As diagnostic tool. J Pharm Bioallied Sci. 118–127
4. Chauvin, M., Larsen, M., Quirant, B., Quentric, P., Dorgham, K., Royer, L., ... & Sauce, D. (2021). Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients. Frontiers in cellular and infection microbiology, 764.
About the author
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Dajana Domik
Dr. Dajana Domik joined Tecan in 2020 as a product manager responsible for the saliva portfolio as well as diverse other products, e.g. Immunology. Dajana has a scientific background and spent time in the USA as a postdoc and is now supporting the Global Reagent Marketing & Support Department with immunoassay solutions at Tecan.