Expression of biomarkers of interferon type I in patients suffering from chronic diseases

Abstract

Interferons (IFNs) are used widely in the treatment of viral infections, tumours and neurological disorders. The aim of this study was to evaluate the endogenous expressions of various IFN-induced compounds [specifically: neopterin (NPT), beta2microglobulin (beta2mg) and 2-5 oligoadenylate synthetase (2-5 OAS)] in patients with various chronic diseases requiring treatment with IFN type I. The results showed that patients with such chronic diseases as hepatitis C virus-associated type II mixed cryoglobulinaemia (MC), chronic hepatitis C (CHC) and relapsing-remitting multiple sclerosis (RRMS) are characterized by different activations of the IFN system. Furthermore, the interindividual variability in baseline levels of IFN-induced biomarkers was higher in patients with chronic diseases than in healthy individuals. When levels of the above biomarkers were measured 24 h after the first injection of IFN in patients with CHC or RRMS, significant increases in expression levels of IFN-induced compounds were recorded but, again, there is a broad range of variability in the degree of increase. Further, a significant inverse correlation between baseline levels of NPT, beta2mg and 2-5 OAS activity and their relative increases after IFN administration was found in patients with CHC or RRMS. Together, the results are consistent with the observation that there is considerable interindividual heterogeneity in the clinical response to IFNs, which suggests that host factors other than disease markers must be taken into account in order to manage and optimize the IFN therapy.

Fig. 1

Serum level of beta2microglobulin (β2mg) (a), neopterin (NPT) (b) and 2–5 oligoadenylate synthetase activity (2–5 OAS) (c) in patients with relapsing-remitting multiple sclerosis (RRMS, n = 30), chronic hepatitis C (CHC, n = 38), hepatitis C virus (HCV)-associated type II mixed cryoglobulinaemia (MC, n = 37). Ten healthy individuals were also examined. All blood samples were obtained from patients who were included for interferon (IFN) therapy within 1–7 days of the starting date. *β2mg (a) MC versus CHC, RRMS and healthy controls, P < 0·05; NPT (b) MC versus CHC, RRMS and healthy controls, P < 0·05; RRMS versus CHC and healthy controls, P < 0·05; 2–5 OAS (c) MC versus RRMS and healthy controls, P < 0·05; CHC versus RRMS and healthy controls P < 0·05.

Fig. 2

Variability of expression of beta2microglobulin (β2mg) (a), neopterin (NPT) (b) and 2–5 oligoadenylate synthetase activity (2–5 OAS) (c) in patients with relapsing-remitting multiple sclerosis (RRMS, n = 30), chronic hepatitis C (CHC, n = 38) and hepatitis C virus (HCV)-associated type II mixed cryoglobulinemia (MC, n = 37) prior to commencement of interferon (IFN) therapy. The coefficient of variation (CV) was used to measure interpatient variability in blood concentrations of IFN-induced biomarkers.