suPAR as a biomarker for infectious diseases

The suPAR level is elevated in patients with infectious diseases compared with healthy individuals. An elevated level is associated with:

• Advanced disease
• Poor prognosis

This applies to various infectious diseases including, but not limited to:

• HIV^1-5,25
• Sepsis^6-11
• Hepatitis B¹²
• Hepatitis C^13-14
• Tuberculosis^15-17
• Malaria^18-19
• Meningitis^21-22
• Pneumonia^23-24

In general, the suPAR level is elevated in patients with infectious diseases. In all infectious diseases studied, an elevated suPAR level is associated with a poorer prognosis. In infectious diseases the prognostic value of suPAR is strong.

HIV

In patients with HIV infection, it was demonstrated that the suPAR level is slightly elevated and increases with the disease stage (WHO criteria). The first study of suPAR in HIV showed that suPAR was at least as strong a prognostic marker of the natural progression of HIV, as CD4 and viral load¹. Antiretroviral therapy (ART) causes a decrease in suPAR of about 17%². However, after five years of treatment, the patients’ suPAR level is still higher than in healthy controls². Side effects of treatment are associated with higher suPAR levels³. In addition to correlating with virological and immunological effects of the infection, the suPAR level correlates with age, metabolic syndrome, smoking, and low muscle mass⁴. In HIV patients with ART-induced viral suppression, suPAR is a superior and independent predictor of non-AIDS-related comorbidities (e.g. cardiovascular and renal diseases).

Sepsis

In patients with sepsis^5-7, it has been found that the suPAR level is of some diagnostic value, as it increases with the seriousness of sepsis and frequently is above 10 ng/mL in patients with impaired organ function^8,9. However, most studies show that CRP and procalcitonin (PCT) are better diagnostic markers of bacterial sepsis, whereas suPAR is the best prognostic marker^6,10. In a later cohort, it was validated that suPAR in combination with the APACHE score can improve risk stratification of patients with sepsis¹¹.

Hepatitis

The suPAR level is elevated in hepatitis B patients with hepatic fibrosis compared to patients with no or mild fibrosis. Thus, suPAR may be useful for identification of hepatitis B patients with significant fibrosis¹².

In hepatitis C patients the suPAR level is elevated, and the level increases with the severity of fibrosis. Because hepatic disease and fibrosis affect the suPAR level, the prognostic value and the reflection of disease severity are probably a result of the liver condition rather than the hepatitis C infection¹³. This is supported by data demonstrating that suPAR is also associated with seriousness and prognosis in patients with non-alcoholic fatty liver disease (NASH)¹⁴.

Tuberculosis

Active tuberculosis (TB) causes a substantial increase in the suPAR level, typically to about 6-7 ng/mL – the higher, the worse^15,16. A study from Guinea-Bissau has shown that the suPAR level measured upon initiation of treatment for TB is a prognostic marker of mortality during treatment. Measurement of suPAR following one month of treatment demonstrated that the change in suPAR level was also associated with mortality; patients experiencing no decrease – or even an increase – in suPAR level have a poorer prognosis than patients experiencing a decrease following one month of treatment¹⁷.

Malaria

suPAR has been studied in children, adults, and pregnant women with malaria. In children, a doubling of the suPAR level is observed, which decreases back to a normal level following 14 days of effective treatment¹⁸. In adult patients with malaria and acute renal damage, suPAR was associated with the severity of the renal damage and was higher in patients who subsequently needed dialysis¹⁹. For pregnant women infected with malaria, a high suPAR level is associated with the low birth weight of the baby²⁰.

CSF

An elevated suPAR level in the cerebrospinal fluid (CSF) in children and adults with meningitis is associated with increased mortality^21,22.

Pneumonia

In children with pneumonia, suPAR is associated with the severity of the infection and length of hospital stay²³. In adults with sepsis and ventilator-associated pneumonia, the suPAR level is strongly and independently associated with a negative prognosis²⁴.

Covid-19

Read more about suPAR and COVID-19 on here.