Abstract
Inflammation is thought to be involved in the pathogenesis of autism spectrum disorder (ASD). Pteridine metabolites are biomarkers of inflammation that increase on immune system activation. In this study, we investigated the urinary pteridine metabolites in ASD patients as a possible biomarker for immune activation and inflammation. This observational, cross-sectional, prospective study collected urine samples from 212 patients with ASD and 68 age- and sex-matched healthy individuals. Urine neopterin (NE) and biopterin (BIO) levels were measured. Patients who had chronic disorders, active infection at the time of sampling, or high C-reactive protein levels were excluded. The urine NE and BIO concentrations were determined by high-performance liquid chromatography. The ratios of both NE and BIO to creatinine (CRE) were used to standardise the measurements. The NE/CRE and NE/BIO levels were significantly higher in ASD patients than controls. Univariate and multivariate models revealed a significant increase in NE/CRE and NE/BIO in ASD patients. There was a significant relationship between the NE/BIO [average area under the curve (AUC) = 0.717; range: 0.637–0.797] and NE/CRE (average AUC = 0.756; range: 0.684–0.828) ratios, which distinguished individuals with ASD from controls. The elevated NE/CRE and NE/BIO ratios suggest that inflammation and T cell-mediated immunity are involved in the pathophysiology of autism. NE/BIO could serve as a diagnostic inflammatory marker in the pathogenesis of ASD.
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Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- ACN:
-
Acetonitrile
- ASD:
-
Autism spectrum disorders
- BIO:
-
Biopterin
- CNS:
-
Central Nervous System
- CRE:
-
Creatinine
- CRP:
-
C-reactive protein
- GTP:
-
Guanosine triphosphate
- GTPCH:
-
Guanosine triphosphate – cyclohydrolase
- HPLC:
-
High – Pressure Liquid Chromatography
- IFN –γ:
-
Interferon gamma
- LoD:
-
Limit of Detection
- LoQ:
-
Limit of Quantification
- MS:
-
Multiple sclerosis
- NAOH:
-
Sodium hydroxide
- NE:
-
Neopterin
- PT:
-
Pterin
- PTPS:
-
6 – pyrovoyl – tetrahydropterin synthase
- ROC:
-
Receiver Operating Characteristics
- SPSS:
-
Statistical Package for the Social Sciences
- TRIS – HCl:
-
Tri-hydroxymethyl-aminomethane-hydrochloride
- TNF –α:
-
Tumor necrosis factor alpha
- 6PTC:
-
Pterin-6-carboxylic acid
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All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version.
1. E.O.E: Conceptualization, Formal analysis, Investigation, Resources, Writing Original Draft, Project administration.
2. E.I: Validation, Resources.
3. M.S.C.: Resources, Data Curation.
4. T.Z.: Validation, Writing—Original Draft.
5. G.Y.: Writing—Review & Editing.
6. M.N.C.: Writing—Review & Editing.
7. C.A.Z.: Conceptualization, Methodology, Writing—Review & Editing, Project administration and manuscript.
8. E.K.: Writing—Review & Editing, Supervision.
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Oge-Enver, E., Isat, E., Cansever, M.S. et al. Urinary neopterin and biopterin indicate that inflammation has a role in autism spectrum disorder. Metab Brain Dis 38, 2645–2651 (2023). https://doi.org/10.1007/s11011-023-01287-3
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DOI: https://doi.org/10.1007/s11011-023-01287-3