Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis
Date
2022
Authors
Shepheard, S.R.
Karnaros, V.
Benyamin, B.
Schultz, D.W.
Dubowsky, M.
Wuu, J.
Chataway, T.
Malaspina, A.
Benatar, M.
Rogers, M.L.
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Journal article
Citation
European Journal of Neurology, 2022; 29(4):990-999
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Abstract
<h4>Background and purpose</h4>The aim was to evaluate urinary neopterin, a marker of pro-inflammatory state, as a potential biomarker of disease prognosis and progression in amyotrophic lateral sclerosis (ALS); and to compare its utility to urinary neurotrophin receptor p75 extracellular domain (p75<sup>ECD</sup> ).<h4>Methods</h4>This was an observational study including 21 healthy controls and 46 people with ALS, 29 of whom were sampled longitudinally. Neopterin and p75<sup>ECD</sup> were measured using enzyme-linked immunoassays. Baseline and longitudinal changes in clinical measures, neopterin and urinary p75<sup>ECD</sup> were examined, and prognostic utility was explored by survival analysis.<h4>Results</h4>At baseline, urinary neopterin was higher in ALS compared to controls (181.7 ± 78.9 μmol/mol creatinine vs. 120.4 ± 60.8 μmol/mol creatinine, p = 0.002, Welch's t test) and correlated with the Revised ALS Functional Rating Scale (r = -0.36, p = 0.01). Combining previously published urinary p75<sup>ECD</sup> results from 22 ALS patients with a further 24 ALS patients, baseline urinary p75<sup>ECD</sup> was also higher compared to healthy controls (6.0 ± 2.7 vs. 3.2 ± 1.0 ng/mg creatinine, p < 0.0001) and correlated with the Revised ALS Functional Rating Scale (r = -0.36, p = 0.01). Urinary neopterin and p75<sup>ECD</sup> correlated with each other at baseline (r = 0.38, p = 0.009). In longitudinal analysis, urinary neopterin increased on average (±SE) by 6.8 ± 1.1 µmol/mol creatinine per month (p < 0.0001) and p75<sup>ECD</sup> by 0.19 ± 0.02 ng/mg creatinine per month (p < 0.0001) from diagnosis in 29 ALS patients.<h4>Conclusion</h4>Urinary neopterin holds promise as marker of disease progression in ALS and is worthy of future evaluation for its potential to predict response to anti-inflammatory therapies.
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Data source: Supplementary information, https://doi.org/10.1111/ene.15237
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Copyright 2021 Wiley-Blackwell Publishing
Access Condition Notes: Accepted manuscript available on Open Access