The Effect of Etanercept Therapy on Adrenal Steroid Metabolism in Juvenile Idiopathic Arthritis: A Steroid Metabolomics Approach

Objective To evaluate the impact of anti-tumor necrosis factor-alpha (TNFα: etanercept [Enbrel®]) on adrenal activity in the acute phase of juvenile idiopathic arthritis (JIA) during which there is a decrease in adrenal androgen and cortisol levels. Method Eleven JIA patients aged 12±6.2 years with a disease duration of 6.3±5.2 years were enrolled. They were treated once weekly with etanercept (0.8 mg/kg) for 3±2.8 years. Urine samples for gas chromatography-mass spectrometry steroid hormone analysis were collected before, and 1 and 3 days after etanercept injection and compared to age- and sex-matched healthy control. Results The levels of 23 of the 35 metabolites were low before etanercept treatment. Those 23 metabolites included 2 C19 steroids (androgens), 3 C21 steroid hormone intermediates, 14 cortisol metabolites, 2 corticosterone metabolites and 2 C18 steroids (estrogens). One day post-treatment, only 5 of the 23 metabolite levels remained low. They included 2 C19 metabolites, 2 21 steroid metabolites and 1 cortisol metabolite b-c. Three days post-treatment, the only metabolite levels that continued to be low were 1 C19 metabolite, 2 C21 steroid hormone intermediates and 1 cortisol metabolite (a-Cl), while the remaining 18 metabolites had already normalized after 1 day. DHEAS and 17 OH pregnenolone metabolite levels were the last ones to recover. Urinary metabolite ratios reflecting CYP21 and 11β-HSD2 enzymatic activities were lower in JIA patients than in controls. Conclusion Almost all of the pre-etanercept treatment cortisol urinary metabolite levels were significantly lower than normal, and almost all rose to normal values by 1 day post-treatment. Blocking TNFα restores adrenal function in JIA.

Machine learning approaches to predict gestational age in normal and complicated pregnancies via urinary metabolomics analysis

The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.

Comparison between Prostaglandin E-major urinary metabolite and C-reactive protein levels to reflect endoscopic scores in patients with ulcerative colitis

Prostaglandin E-major urinary metabolite (PGE-MUM) and C-reactive protein (CRP) are useful biomarkers in patients with ulcerative colitis. However, whether changes in endoscopic scores over time are reflected in the values of these biomarkers has not been verified. This prospective observational study aimed to assess the relationship between changes in biomarker levels and endoscopic scores in patients with ulcerative colitis. A total of 100 colonoscopy intervals of patients with ulcerative colitis were enrolled. The relationship between variations in the Mayo endoscopic subscore over time and the accompanying changes in biomarker values were investigated. PGE-MUM levels showed a significant rise in the increased endoscopic score group (P = 0.007) and a decrease with reduced endoscopic score group (P = 0.023). CRP levels showed a significant decline with lower endoscopic values (P < 0.001); however, there was no corresponding increase with higher endoscopic scores (P = 0.141). Biomarker levels remained unchanged with stable endoscopic scores (P = 0.090 and P = 0.705). PGE-MUM levels varied significantly, and corresponded to the mucosal healing state (P = 0.019 and P = 0.009). The correlation between changes in PGE-MUM and the endoscopic score was stronger than that for CRP (r = 0.518, P < 0.001 vs. r = 0.444, P < 0.001, respectively). PGE-MUM reflected changes in endoscopic scores more accurately than CRP.