Çocukluk çağı otoimmün santral sinir sistemi hastalıklarında serum ve idrar örneklerinde neopterin ve serum kinürenin-triptofan yolağı ürünleri düzeylerinin karşılaştırılması.

Abstract

Yıldız Kayaoğlu M, Comparison of the levels of neopterin in serum and urine samples and serum kinürenine-tryptophan pathway products in childhood autoimmune central nervous system diseases, Child Health and Diseases Thesis, Ankara, 2021. Inflammatory demyelinating diseases of the central nervous system (CNS) in childhood include clinically and radiologically defined diseases such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), MOG-antibody related disease and autoimmune encephalitis. In addition certain cases not meeting diagnostic criteria remain without specific diagnosis. Laboratory findings to guide the physician in the diagnosis and management of autoinflammatory diseases of CNS in childhood are needed. Variables called “biomarker” are objectively measurable characters that can be reliably used for diagnosis, grading, prognosis or monitoring of a clinical condition. A good biomarker should be easily measurable in body fluids such as urine, serum, cerebrospinal fluid (CSF). Previous studies suggest serum kynurenine-tryptophan pathway products and serum neopterin as biomarkers for CNS autoimmune diseases. Although neopterins have been studied in various CNS diseases, the number of studies especially in childhood CNS autoimmune disorders is limited. In addition, previous evidence indicates urine as a reliable source for analysis of these products, with the additional advantage of easy sampling increasing patient compliance. This study aimed to measure and compare serum and urine kynurenine-tryptophan pathway products molecules in autoimmune demyelinating diseases of CNS. We studied 27 pediatric multiple sclerosis (pMS) patients, 10 myelin oligodendrocyte glycoprotein (MOG) antibody positive (MOG Ab+) patients, 5 neuromyelitis optica (NMO) patients, and 13 healthy or non-demyelinating disease patients, totally 55 children. Consent was obtained from patients and parents. Neopterin, biyopterin and creatinine in urine, kynurenine and tryptophan in serum were measured by high performance liquid chromatography (HPLC), and neopterin in serum by ELISA method. Statistical analyzes were performed using SPSS (IBM SPSS Statistics 23) package program. The median age of the patients was 15 (5) and the mean age of the control cases was 13.69 ± 2.72 years. The ages of the patients differed significantly between diagnostic groups (p=0,001). The Bonferroni test indicated pMS patients were older than the other groups, siginificantly so from MOG Ab+ patients. The youngest age group was MOG Ab+ patients. When the whole patient group was compared with the controls, a significant difference was found between urinary neopterin values (p=0.006). The cut-off point was determined by ROC analysis: An urinary neopterin value above 167.75 µmol/mol creatinine could distinguish the patients from the controls with a sensitivity of 71%, and specificity of 90%. Comparison for biomarkers between all diagnostic groups showed a significant difference in urinary neopterin values (p=0.002). When examined with the Bonferroni test, it was observed that urinary neopterin values of pMS patients were different from NMO patients, MOG Ab+ patients and controls. The difference was caused by the pMS patient group, the most significant difference being between the pMS group and the control group. There was no difference between pMS patients who were in an attack or stable, but there was a difference in urinary neopterin values of pMS patients (whether in an attack or in a stable state), compared to controls (p=0.002). Therefore urinary neopterin appeared as a biomarker that could differentiate pMS from other demyelinating patient groups, MOG Ab+ patients and NMO patients as well as from controls. The fact that pteridine pathway products had not been studied in urine and serum in children with demyelinating disease before highlights the novelty of this study. If further research in larger samples confirm the present results, these biomarkers might assist the differential diagnosis of pMS from other demyelinating CNS diseases.

Keywords: Neopterin, Kynurenine, Biopterin, Multiple Sclerosis, Urine, Relapse, Stable, Demyelinating Disease, Neuromyelitis Optica Spectrum Disorder (NMOSD), MOG Antibody Associated Disease, Serum.