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By Dajana Domik
When patients exhibit symptoms common to more than one disease or invading pathogen it is useful to have a universal biomarker that can help you narrow down the potential causes, monitor progress of an ongoing condition, and give you an advanced warning if the condition is going to worsen. In many cases, neopterin is that biomarker. It gives an early warning signal that the patient’s immune system has been triggered—often before disease-specific clinical symptoms have presented themselves. Here we explore neopterin, its origins, and what makes it such an important and universal marker.
From bee larvae to infection biomarker
Pteridines were first isolated in 1889 as pigments from the wings of lepidoptera, which is an order of insects that includes butterflies and moths. The name pteridine derives from the Greek word, pteron, meaning wing. Almost a century later, a new pteridine molecule was isolated from the larvae of bees as well as royal jelly. These new pteridines were eventually named “neopterin” as they promised to begin a new wave of pteridine research. A few years after this discovery, neopterin was isolated from the urine of patients with various diseases and was not present in healthy subjects. This finding led to the hypothesis that neopterin originated from an immune response.
Macrophages are the immune cells responsible for the production of neopterin, a biomarker, which can be an indication of immune system activation.
Further studies revealed that neopterin was produced in response to a much broader range of immune stimuli. In vitro studies revealed that human macrophages produce neopterin when stimulated by interferon-γ, which is released by T-cells upon activation. This means that the presence of neopterin in human blood or urine is associated with the cellular immune response.
The role of neopterin in the immune response
Interferon-γ is associated with antibacterial, antiprotozoal and antifungal activities of macrophages. The close links between interferon-γ and neopterin have influenced much of the neopterin research over the years. This research has linked neopterin to a wide variety of different immune responses involved in the production of interferon-γ and the activation of macrophages.
Diseases where neopterin is elevated
There are four disease areas in particular that can be linked to elevated neopterin levels:
Viral and bacterial infections
Acute viral infections will often induce high neopterin levels, as will infections with intracellular bacteria such as Mycobacteria tuberculosis, M. leprae, or parasites. Neopterin can often be detected very early, before symptoms occur or antibodies are produced. Interestingly, neopterin levels will often be high in the acute stages of infection, but then fall off when antibodies are produced. This means that there is an early diagnostic window during the onset of the infection cycle where a broad test for neopterin is advantageous and might be preferable to a pathogen-specific antibody test.
Monitoring neopterin levels in patients after an allograft procedure can indicate if the graft is being rejected. As an early marker of an immune response, high levels of neopterin in a transplant patient could be the first sign of rejection of the transplant giving critical care physicians more time to intervene.
Neopterin levels are also high in the early stages of autoimmune diseases such as Crohn’s disease, rheumatoid arthritis and ulcerative colitis. The levels of neopterin are also quite closely correlated to the severity and extent of the disease.
Sarcoidosis is a rare condition characterized by the clustering of inflammatory cells in different tissues around the body. The symptoms of the disease vary depending on which tissues have been affected. However, all instances of sarcoidosis are associated with elevated neopterin levels. Neopterin can therefore serve as a useful early indicator of potential sarcoidosis.
Neopterin can tell you a lot ...
Neopterin has been extensively studied and its relationship to the severity and progress of many diseases is well known. However, as has been discussed throughout this article, neopterin is associated with several different roles in the immune response and different disease states. Therefore, when used in combination with disease-specific tests, neopterin testing can add an extra layer of information that can improve clinical decision-making, leading to more favorable outcomes.
… And it can tell you a lot earlier
A common thread through diseases that are associated with increased neopterin levels is that levels tend to be highest during the acute/early stages of the disease. Because neopterin levels are often elevated before clinical symptoms occur, it functions as an early warning sign indicating that something is wrong. Its function as a universal indicator is advantageous. Of course, given that neopterin is associated with so many different diseases or disorders, it can be applied as a first measure and follow-up tests would contribute to a better understanding.
Neopterin in COVID-19
As we have seen, neopterin is increasingly being recognized as an early marker for a wide spectrum of diseases and infections. In particular, recent research1 reveals that it can be a useful marker in monitoring COVID-19 patients to help predict the severity and course of the disease. This will be the subject of the next article in our series.
1. 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
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.