2′,5′-Oligoadenylate Synthetase Activity as a Responsive Marker During Interferon Therapy for Chronic Hepatitis C

Giannelli, Gianluigi; Antonelli, Guido; Fera, G; Dianzani, F.; Schiraldi, O

doi:10.1089/jir.1993.13.57

Cited by 26 publications

(17 citation statements)

References 16 publications

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“…Low levels of this enzyme are probably unable to suppress virus replication successfully. Failure to produce this enzyme has been reported in non-responders [20]. It is likely that a deficit in intraceilular IFN-mediated signalling could be associated with the lack of response.…”

Section: Discussionmentioning

confidence: 94%

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C

Giannelli

Antonelli

Fera

et al. 1994

Clinical and Experimental Immunology

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SUMMARYIt is known that IFN therapy can induce the development of anti-IFN antibodies. In order to evaluate the biological and clinical significance of both neutralizing (NA) and non-neutralizing (binding) antibodies, 123 patients with chronic hepatitis C treated with recombinant IFN-fi were examined. Among them. 15 were positive for NA and 24 for binding antibodies. The kinetics of NA appearance show that, in general, they develop early during the first 3 months of treatment. Moreover. NA seem to be clinically relevant, since they may be responsible for non-responsiveness to treatment in 53% of patients who develop them. The evaluation of the clinical significance of binding antibodies is more difficult. They appear significantly earlier in non-responders than in responders, but no differences were observed in the overall percentage of seroconversion between responders and non-responders. Thus, it is not possible at the moment to establish their possible role in inducing non-responsiveness.

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Section: Discussionmentioning

confidence: 94%

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C

Giannelli

Antonelli

Fera

et al. 1994

Clinical and Experimental Immunology

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“…26,27 Indeed, based on the clinical observation that the serum level of 2-5AS is generally increased in patients on administration of IFN, the serum level of this enzyme has been used as a clinical marker to predict the responsiveness of the host to IFN. 28,29 More recently, IFN regulatory factor 3 was shown to trigger the type I interferon system, i.e., on viral infection, IFN regulatory factor 3 is first phosphorylated and transported into the nucleus as a component of activated transcription factors that induce IFN, and then IFN-induced genes including that for 2-5AS are induced. 30,31 Based on these findings, an increase in serum levels of 2-5AS may reflect the activation of the cellular IFN system.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of soluble interferon alfa/beta receptor as an inhibitory factor of interferon in the patients with chronic hepatitis C

et al. 1999

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Human serum contains a soluble form of interferon alfa/beta (sIFN ␣/␤) receptors, the functional and clinical significance of which has not been investigated in patients with chronic hepatitis C. In the present study, serum levels of sIFN ␣/␤ receptor were assessed in 81 patients with chronic hepatitis C and correlated with the effectiveness of IFN therapy in these patients. Serum levels of sIFN ␣/␤ receptor were significantly higher in patients with chronic hepatitis C than in healthy control patients (P F .0001). In these patients, serum levels of sIFN ␣/␤ receptor were correlated with those of alanine transaminase (ALT) (P F .05), (2Ј-5Ј)serum oligo(A) synthetase (2-5AS) (P F .0001), and pathological stages of liver fibrosis (P F .01). In 55 patients with chronic hepatitis C who underwent IFN therapy, there was an inverse correlation between the pretherapeutic serum levels of sIFN ␣/␤ receptor and the rate of increase in serum levels of 2-5AS after the start of IFN (P F .01). Pretherapeutic serum levels of sIFN ␣/␤ receptor were significantly lower in patients who showed sustained response to IFN therapy compared with those who did not respond to the therapy (P F .05). Multivariate analysis showed that low levels of serum sIFN ␣/␤ receptor (I4.0 ng/mL) (P F .05) and serological hepatitis C virus genotype II (P F .05) were independent variables contributing to sustained response to IFN therapy. Thus, pretherapeutic serum levels of sIFN ␣/␤ receptor were correlated with the effectiveness of IFN therapy, suggesting that sIFN ␣/␤ receptor suppresses the effectiveness of IFN therapy in patients with chronic hepatitis C. (HEPATOLOGY 1999;30:1325-1331.)Type I interferon (IFN) exerts antiviral and antineoplastic activities, and is involved in immunity control. IFN therapy is currently established as the only effective means of eradicating hepatitis C virus (HCV) from hepatic cells in patients with chronic hepatitis C. However, because the rate of complete cure of the disease accompanied by complete disappearance of HCV RNA from peripheral blood is only 30%, the establishment of a more effective regimen for IFN therapy is warranted. IFN exerts its antiviral activity in target cells via binding to receptors anchored on the outer surface of the cell membrane. 1,2 We and other investigators have previously reported that the effectiveness of IFN therapy in patients with chronic hepatitis C is associated with the amount of type I IFN receptor messenger RNA in the liver. [3][4][5][6] Type I IFN receptor has a multichain structure consisting of at least 2 subunits, AR1 and AR2. 7-10 The AR2 subunit of 100 kd is anchored on the outer surface of the cell membrane and mediates intracellular signal transduction. A soluble form of AR2 proteins of 40 kd, designated soluble IFN alfa/beta (sIFN ␣/␤) receptor, is found in body fluids including peripheral blood and urine. 11 Novick et al. 9,11,12 showed that sIFN ␣/␤ receptor molecules inhibited the activity of type I IFN as shown by biological assay with human WISH cells. An IFN-inhi...

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“…IFN is induced by various factors, including viral infections, and is a cytokine possessing biological activities that include anti-viral, anti-tumor and immunomodulatory activities [1,2,6,8,11,12]. IFN induced by viral infections activates three enzymes-2'-phosphodiesterase, 2,5A-S and phosphokinase -which stimulate anti-viral activity via independent pathways [1].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we examined 2'-5'oligoadenylate synthetase (2,5A~S) activity [1,2,6,8,11,12], one of the parameters indicating the anti-viral activity of IFN, to investigate the relationship between the suppression of viral proliferation and prognosis and to study the possible pathogenesis of IS SHL.…”

Section: Introductionmentioning

confidence: 99%

Alpha-interferon for the treatment of idiopathic sudden sensorineural hearing loss

Kanemaru

Fukushima

Nakamura

et al. 1997

Eur Arch Otorhinolaryngol

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We have employed alpha-interferon (IFN-alpha), an anti-viral agent, in the treatment of severe idiopathic sudden sensorineural hearing loss (ISSHL). Forty-two patients were studied and had an average hearing ability of > or = 70 dB before treatment. We also examined 2'-5' oligoadenylate synthetase (2,5A-S) activity, one of the parameters indicating anti-viral activity of IFN, to investigate the relationship between the suppression of viral proliferation and prognosis and explain the pathogenesis of ISSHL. Complete recovery was found in 27 patients (64.3%) after IFN therapy. Increased 2,5A-S activity was observed on the 3rd day of IFN therapy in 24 of the 27 patients who completely recovered. No severe adverse events were reported after IFN therapy. Findings suggest that IFN therapy may be effective and safe in the treatment of ISSHL and calls for further investigation.

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2′,5′-Oligoadenylate Synthetase Activity as a Responsive Marker During Interferon Therapy for Chronic Hepatitis C

Cited by 26 publications

References 16 publications

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C

Serum levels of soluble interferon alfa/beta receptor as an inhibitory factor of interferon in the patients with chronic hepatitis C

Alpha-interferon for the treatment of idiopathic sudden sensorineural hearing loss

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