Christian Lunetta1, Andrea Lizio2, Francesca Gerardi2, Claudia Tarlarini2, Massimo Filippi3, Nilo Riva3, Lucio Tremolizzo4, Susanna Diamanti4, Cinzia Carla Dellanoce5, Lorena Mosca6, Valeria Ada Sansone2,7, Jonica Campolo5. 1. NEuroMuscular Omnicentre, Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy. christian.lunetta@centrocliniconemo.it. 2. NEuroMuscular Omnicentre, Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy. 3. Neuropathology Unit, Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. 4. ALS Clinic, Neurology Unit, San Gerardo Hospital, and University of Milano-Bicocca, Monza, Italy. 5. CNR Institute of Clinical Physiology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 6. Department of Laboratory Medicine, Medical Genetics, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 7. Department of Biomedical Sciences of Health, University of Milan, Milan, Italy.
Abstract
OBJECTIVE: To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS. METHODS: We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALS patients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival. RESULTS: Urinary neopterin was significantly higher in pALS (263.90 [198.71-474.90]) compared to MS (155.28 [131.74-190.38], p = < .001), OND patients (205.60 [158.96-299.41], p = 0.04) and HC (169.55 [134.91-226.10], p < .001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r = - 0.46, p < .001) and its subscores (bulbar r = - 0.34, p = 0.002; motor r = - 0.33, p = 0.003; respiratory r = - 0.53, p < .001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation. CONCLUSIONS: Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin's potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.
OBJECTIVE: To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS. METHODS: We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALSpatients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival. RESULTS: Urinary neopterin was significantly higher in pALS (263.90 [198.71-474.90]) compared to MS (155.28 [131.74-190.38], p = < .001), OND patients (205.60 [158.96-299.41], p = 0.04) and HC (169.55 [134.91-226.10], p < .001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r = - 0.46, p < .001) and its subscores (bulbar r = - 0.34, p = 0.002; motor r = - 0.33, p = 0.003; respiratory r = - 0.53, p < .001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation. CONCLUSIONS: Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin's potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.