Clinical evaluation of plasma neopterin as a biomarker of immune activation in allergic rhinitis using a fluorescence-based o-phthaldehyde derivatization method

采用基于荧光法的邻苯二甲醛衍生化方法对血浆新蝶呤作为过敏性鼻炎免疫激活生物标志物进行临床评价

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Abstract

Allergic rhinitis (AR) is a common chronic inflammatory condition of the nasal mucosa driven by IgE-mediated hypersensitivity, yet reliable biomarkers of systemic immune activity and oxidative stress remain limited despite involvement of Th2 cytokines, eosinophils, and macrophages. Neopterin (NPT) is a macrophage-derived marker of interferon-γ-induced immune activation and oxidative imbalance, but current plasma detection methods are expensive, or lack sufficient sensitivity for routine clinical use. Herein, a validated fluorescence-based method was developed for determination of plasma NPT using o-phthaldehyde derivatization in the presence of 2-mercaptoethanol under mildly alkaline conditions. The reaction formed a stable isoindole derivative with strong fluorescence (λ_ex = 335 nm, λ_em = 455 nm), increasing the quantum yield from 0.24 for native NPT to 0.65 for the NPT-OPA product. The method showed linearity from 1 to 20 ng/mL (r² = 0.9996), with a detection limit of 0.22 ng/mL and a quantification limit of 0.66 ng/mL. Accuracy ranged from 99.0% to 100.8%, and precision remained below 1.0%. No interference appeared from biopterin, folic acid, riboflavin, or xanthopterin, each contributing less than 5% of the NPT signal. Plasma NPT was measured in 26 AR patients and 26 healthy controls. AR patients showed elevated NPT concentrations (2.9 ± 0.7 ng/mL) compared to controls (1.5 ± 0.3 ng/mL, p < 0.001). NPT levels correlated with symptom severity (r = 0.44, p = 0.015) and eosinophil counts (r = 0.41, p = 0.022), indicating an association between immune activation and disease intensity. The fluorescence-based method provides a sensitive, selective, and rapid approach for plasma NPT quantification and supports NPT as a potential biomarker of immune activation and oxidative stress in AR.

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