Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis p
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RESEARCH
Open Access
Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients Valentina Durastanti1*, Alessandra Lugaresi2, Placido Bramanti3, Mariapia Amato4, Paolo Bellantonio5, Giovanna De Luca2, Orietta Picconi6, Roberta Fantozzi7, Laura Locatelli8, Annalisa Solda’9, Edoardo Sessa3, Rocco Totaro10, Silvia Marino3, Valentina Zipoli4, Marino Zorzon8 and Enrico Millefiorini11
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 (IFNb-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 IFNb-1a over a period of 24 months. Methods: RRMS patients (n = 101) received open-label IFNb-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 IFNb administration the clinical relevance of these findings needs to be confirmed with more detailed studies.
Background In multiple sclerosis (MS) patients, IFNb-1a reduces clinical and imaging signs of disease activity, ultimately delaying the progression of physical disability [1,2]. However, a relatively long-term follow-up is necessary for changes in physical disability scores to become evident. Although magnetic resonance imaging (MRI) * Correspondence: [email protected] 1 Department of Neurological Sciences, University “La Sapienza”, Viale dell’Università, 30, 00185, Rome, Italy Full list of author information is available at the end of the article
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