Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients

Valentina Durastanti, Alessandra Lugaresi, Placido Bramanti, Mariapia Amato, Paolo Bellantonio, Giovanna De Luca, Orietta Picconi, Roberta Fantozzi, Laura Locatelli, Annalisa Solda', Edoardo Sessa, Rocco Totaro, Silvia Marino, Valentina Zipoli, Marino Zorzon, Enrico Millefiorini

Research output: Contribution to journalArticle

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Abstract

Background: Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered in vitro markers of interferon beta-1a (IFNβ-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNβ-1a over a period of 24 months.Methods: RRMS patients (n = 101) received open-label IFNβ-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests.Results: Neopterin (p <0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p <0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p <0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation.Conclusions: Although differences in serum markers concentration were found following IFNβ administration the clinical relevance of these findings needs to be confirmed with more detailed studies.

Original languageEnglish
Article number42
JournalJournal of Translational Medicine
Volume9
DOIs
Publication statusPublished - Apr 18 2011

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Neopterin
Kynurenine
Tryptophan
Multiple Sclerosis
Degradation
Relapsing-Remitting Multiple Sclerosis
Therapeutics
Neutralizing Antibodies
Biomarkers
Interferon beta-1a
Analysis of variance (ANOVA)
Labels
Analysis of Variance
Recurrence
Injections

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients. / Durastanti, Valentina; Lugaresi, Alessandra; Bramanti, Placido; Amato, Mariapia; Bellantonio, Paolo; De Luca, Giovanna; Picconi, Orietta; Fantozzi, Roberta; Locatelli, Laura; Solda', Annalisa; Sessa, Edoardo; Totaro, Rocco; Marino, Silvia; Zipoli, Valentina; Zorzon, Marino; Millefiorini, Enrico.

In: Journal of Translational Medicine, Vol. 9, 42, 18.04.2011.

Research output: Contribution to journalArticle

Durastanti, V, Lugaresi, A, Bramanti, P, Amato, M, Bellantonio, P, De Luca, G, Picconi, O, Fantozzi, R, Locatelli, L, Solda', A, Sessa, E, Totaro, R, Marino, S, Zipoli, V, Zorzon, M & Millefiorini, E 2011, 'Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients', Journal of Translational Medicine, vol. 9, 42. https://doi.org/10.1186/1479-5876-9-42
Durastanti, Valentina ; Lugaresi, Alessandra ; Bramanti, Placido ; Amato, Mariapia ; Bellantonio, Paolo ; De Luca, Giovanna ; Picconi, Orietta ; Fantozzi, Roberta ; Locatelli, Laura ; Solda', Annalisa ; Sessa, Edoardo ; Totaro, Rocco ; Marino, Silvia ; Zipoli, Valentina ; Zorzon, Marino ; Millefiorini, Enrico. / Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients. In: Journal of Translational Medicine. 2011 ; Vol. 9.
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AU - Durastanti, Valentina

AU - Lugaresi, Alessandra

AU - Bramanti, Placido

AU - Amato, Mariapia

AU - Bellantonio, Paolo

AU - De Luca, Giovanna

AU - Picconi, Orietta

AU - Fantozzi, Roberta

AU - Locatelli, Laura

AU - Solda', Annalisa

AU - Sessa, Edoardo

AU - Totaro, Rocco

AU - Marino, Silvia

AU - Zipoli, Valentina

AU - Zorzon, Marino

AU - Millefiorini, Enrico

PY - 2011/4/18

Y1 - 2011/4/18

N2 - Background: Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered in vitro markers of interferon beta-1a (IFNβ-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNβ-1a over a period of 24 months.Methods: RRMS patients (n = 101) received open-label IFNβ-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests.Results: Neopterin (p <0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p <0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p <0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation.Conclusions: Although differences in serum markers concentration were found following IFNβ administration the clinical relevance of these findings needs to be confirmed with more detailed studies.

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