Decreased serum tryptophan levels in patients with MOGAD:a cross-sectional survey.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of central nervous system (CNS). Tryptophan indole catabolites have been reported to associate with the inflammatory diseases of the CNS. However, the roles of tryptophan indole catabolites have been rarely elucidated in MOGAD. METHODS: This cross-sectional study enrolled forty MOGAD patients, twenty patients with other non-inflammatory neurological diseases (OND) and thirty-five healthy participants. Serum and cerebrospinal fluid (CSF) samples of MOGAD and OND subjects during clinical attacks, serum samples of healthy participants were obtained. The concentrations of tryptophan, indoleacetic acid (IAA), indoleacrylic acid (IA) and indole-3-carboxylic acid (I-3-CA) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The correlations between tryptophan indole catabolites and maintenance immunotherapy, disease duration, overall numbers of attacks, short-term outcome in MOGAD patients were investigated. RESULTS: Levels of serum tryptophan, IAA, IA and CSF tryptophan in MOGAD patients were significantly decreased, while levels of serum I-3-CA and CSF IA were markedly increased compared with OND patients and healthy controls. Levels of serum tryptophan, CSF tryptophan and IA were significantly decreased in MOGAD patients who had received maintenance immunotherapy within 6 months before the attack. In MOGAD patients, serum and CSF tryptophan conversely correlated with disease duration and overall numbers of attacks, and serum IA negatively correlated with disease duration. Furthermore, serum tryptophan in MOGAD patients negatively correlated with the modified Rankin Scale (mRS) scores at 3 months. CONCLUSION: This study manifested decreased serum tryptophan levels and serum tryptophan may be the potential marker to predict the short-term outcome in MOGAD patients.

Profile and potential role of novel metabolite biomarkers, especially indoleacrylic acid, in pathogenesis of neuromyelitis optica spectrum disorders.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory and demyelinating disorder that can lead to serious disability and mortality. Humoral fluid biomarkers with specific, convenient, and efficient profiles that could characterize and monitor disease activity or severity are very useful. We aimed to develop a sensitive and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS)/MS-based analytical method for novel biomarkers finding in NMOSD patients and verified its function tentatively. Methods: Serum samples were collected from 47 NMOSD patients, 18 patients with other neurological disorders (ONDs), and 35 healthy controls (HC). Cerebrospinal fluid (CSF) samples were collected from 18 NMOSD and 17 OND patients. Three aromatic amino acids (phenylalanine, tyrosine, and tryptophan) and nine important metabolites that included phenylacetylglutamine (PAGln), indoleacrylic acid (IA), 3-indole acetic acid (IAA), 5-hydroxyindoleacetic acid (HIAA), hippuric acid (HA), I-3-carboxylic acid (I-3-CA), kynurenine (KYN), kynurenic acid (KYNA), and quinine (QUIN) were analyzed by using the liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method. The profile of IA was further analyzed, and its function was verified in an astrocyte injury model stimulated by NMO-IgG, which represents important events in NMOSD pathogenesis. Results: In the serum, tyrosine and some of the tryptophan metabolites IA and I-3-CA decreased, and HIAA increased significantly in NMOSD patients. The CSF levels of phenylalanine and tyrosine showed a significant increase exactly during the relapse stage, and IA in the CSF was also increased markedly during the relapse and remission phases. All conversion ratios had similar profiles with their level fluctuations. In addition, the serum IA levels negatively correlated with glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) levels in the serum of NMOSD patients were measured by using ultra-sensitive single-molecule arrays (Simoa). IA showed an anti-inflammatory effect in an in vitro astrocyte injury model. Conclusion: Our data suggest that essential aromatic amino acid tryptophan metabolites IA in the serum or CSF may serve as a novel promising biomarker to monitor and predict the activity and severity of NMOSD disease. Supplying or enhancing IA function can promote anti-inflammatory responses and may have therapeutic benefits.

Circulating choline pathway nutrients and risk of moyamoya disease.

Background: Circulating choline pathway nutrients play a critical role in first stroke and recurrent stroke. However, there is limited information available on the effects of choline pathway nutrients on the risk of moyamoya disease (MMD) and its subtypes. We investigated the association between circulating choline and betaine and the incident risk of MMD and its subtypes. Methods: The case-control study enrolled 385 patients with MMD [i.e., 110 transient ischemic attack (TIA)-type MMD, 157 infarction-type MMD, and 118 hemorrhagic-type MMD] and 89 matched healthy controls. Results: Serum choline and betaine were inversely related to the risk of MMD and its subtypes. The risk of MMD was decreased with each increment in choline level [per 1 µmol increase: odds ratio (OR), 0.756; 95% CI, 0.678-0.843] and betaine level (per 1 µmol increase: OR, 0.952; 95% CI, 0.932-0.972), respectively. When choline and betaine were assessed as quartiles, compared with the lowest quartile of serum choline and betaine levels, those in the highest quartile had a significantly decreased risk of MMD (choline, Q4 vs. Q1: OR, 0.023; 95% CI, 0.005-0.118; betaine, Q4 vs. Q1: OR, 0.058; 95% CI, 0.018-0.184). Conclusions: Serum choline and betaine were associated with the decreased risk of MMD and its subtypes.