Supplementary Material for: Skin-Homing IL-13-Producing T Cells Expand in the Circulation of Patients with Drug Rash with Eosinophilia and Systemic Symptoms

<p><b><i>Background:</i></b> Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is characterized by severe drug-induced reactions with extensive cutaneous lesions and visceral involvement. Although T cell-mediated hypersensitivity reactions to drugs may be involved in the pathogenesis of DRESS, there is limited data regarding the T-cell phenotypes responsible for the pathogenesis of DRESS. <b><i>Objective and Methods:</i></b> Using flow cytometry, we investigated the cytokine profiles and cutaneous lymphocyte antigen (CLA) expression in circulating T cells in patients with DRESS. <b><i>Results:</i></b> The proportions of circulating IL-4- and IL-13-producing CD4+ T cells, but not CD8+ T cells, were significantly higher in patients with DRESS during the active stage of the disease than in healthy subjects, and these proportions declined during the recovery stage. No differences in the proportions of circulating IFN-γ-, IL-17-, and IL-22-producing CD4+ and CD8+ T cells were observed between patients with DRESS and healthy subjects. A strong correlation between the proportion of IL-13-producing CD4+ T cells and serum levels of thymus and activation-regulated chemokine was observed. The proportion of CLA-expressing CD4+ T cells was significantly higher during the active stage of the disease. Moreover, the proportion of IL-13-producing CD4+ T cells was higher in the CLA+ subset than in the CLA- subset. <b><i>Conclusions:</i></b> Skin-homing IL-13-producing CD4+ T cells may be involved in the pathogenesis of DRESS.</p

Supplementary Material for: A Novel Ataxic Mutant Mouse Line Having Sensory Neuropathy Shows Heavy Iron Deposition in Kidney

<p><b><i>Background/Aims:</i></b> A novel ataxic mouse line was established from the offspring of a male mouse administered cyclophosphamide in a juvenile period. <b><i>Methods:</i></b> We have attempted to examine the phenotype and histopathological changes of affected mice. Furthermore, linkage analysis and sequencing of the mutant was performed to reveal the causative gene locus. <b><i>Results and Conclusion:</i></b> The affected mouse was characterized by heavy hind limb ataxia with gait disorder, which was first recognized at about 4 weeks of age and slowly progressed with advancing age. The phenotype was inherited in an autosomal recessive pattern. The genetic locus associated with the phenotype was named <i>hak</i> and mapped to 107,305,356-108,637,615 on chromosome 2qE3, non-coding sequences in the vicinity of <i>Bdnf</i> gene. Many spheroids were noticed in the cerebellar medulla and the brain stem. In the peripheral nerves, some sensory ganglionic cells showed deposition of NF-200 in the perikaryon and NF-200-positive spheroids in nerve fibers. No inflammatory cell infiltration was observed. In addition, the adult affected mouse had distinct iron deposition in the kidney and the liver, but not in the heart, the skeletal muscle and the central nervous system. These results suggest that the <i>hak</i> mouse has a tissue-specific impairment in the expression of a type of <i>Bdnf</i> transcripts.</p

Supplementary Material for: Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn's disease

Introduction A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index > 150 and active colonic lesions were excluded. Results A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP < 3 mg/l (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81), and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00 while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/ml. Discussion/Conclusion LRG can accurately detect and/or exclude the small bowel lesions by two cut-off values

Supplementary Material for: Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn's disease

Introduction A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index > 150 and active colonic lesions were excluded. Results A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP < 3 mg/l (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81), and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00 while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/ml. Discussion/Conclusion LRG can accurately detect and/or exclude the small bowel lesions by two cut-off values

Supplementary Material for: Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn's disease

Introduction A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index > 150 and active colonic lesions were excluded. Results A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP < 3 mg/l (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81), and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00 while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/ml. Discussion/Conclusion LRG can accurately detect and/or exclude the small bowel lesions by two cut-off values

Supplementary Material for: Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn's disease

Introduction A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index > 150 and active colonic lesions were excluded. Results A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP < 3 mg/l (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81), and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00 while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/ml. Discussion/Conclusion LRG can accurately detect and/or exclude the small bowel lesions by two cut-off values

Supplementary Material for: Optimal use of serum leucine-rich alpha-2 glycoprotein as a biomarker for small bowel lesions of Crohn's disease

Introduction A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index > 150 and active colonic lesions were excluded. Results A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP < 3 mg/l (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81), and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00 while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/ml. Discussion/Conclusion LRG can accurately detect and/or exclude the small bowel lesions by two cut-off values