Neopterin

Neopterin is synthesized by activated monocytes, macrophages, and dendritic cells upon stimulation by interferon gamma produced by T-lymphocytes.^1-3 Neopterin is a nonspecific marker of cellular immune activation and T helper 1 (Th1) type 1 dominated immune response. This molecule is thought to have a role in enhancing macrophage cytotoxicity through interaction with reactive oxygen, nitrogen and chlorides.⁴ Due to its relative stability and ease of assay, serum neopterin measurement has been applied in numerous clinical settings as a means to monitor disease activity or response to therapy.⁵

Neopterin levels are elevated in a number of diseases.⁶ Elevated neopterin levels are found in patients with hepatitis by hepatitis A, B and C infections.⁶ Neopterin levels have been used to predict the course of mycobacterium tuberculosis infection, for differentiating pulmonary tuberculosis from other lung diseases and to monitor the response to anti-tuberculous treatment.⁶ Neopterin has been applied as a diagnostic and prognostic marker in HIV infection.^6-8 Neopterin levels have been shown to predict HIV-related mortality more efficiently than clinical manifestations.^7,8 Successful, highly active antiretroviral therapy is associated with a decrease in neopterin levels.⁶ Neopterin as surrogate marker for viral load to monitor response to antiretroviral treatment in HIV.⁹ More recently, neopterin levels have been measured in COVID-19 patients to estimate disease severity, risk for intensive care unit admission, need for mechanical ventilation and death.¹⁰ Neopterin measurement has been applied to discern the risk of graft rejection.^8,11-12 Furthermore, increased neopterin has been shown to be predictive for risk of mortality in malignancies.^1,13-14

Increased neopterin levels have been shown to predict adverse outcomes in patients with myocardial infarction as well as in individuals with chronic stable angina pectoris.^15-21 Another study found that neopterin was a strong predictor of all-cause and cardiovascular mortality in patients undergoing coronary angiography, regardless of the angiographic findings and regardless of whether or not individuals presented in a stable or unstable condition.²² Neopterin has been shown to predict future events in patients with atherosclerotic disease, independently from the vascular district involved.²³ Neopterin concentrations reflect the severity of the artery disease and can be a marker of plaque instability and of future acute coronary events.²³ Lastly, neopterin is associated with disease severity and is an independent predictor of prognosis in patients with heart failure.^24-26