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Biomedical subjects

Tsutomu Takeuchi

Publications and source records attributed to Tsutomu Takeuchi.

2 recordsLinked to original sources

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age ≤50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article

Muscle Tissue Transcriptome of Idiopathic Inflammatory Myopathy Reflects the Muscle Damage Process by Monocytes and Presence of Skin Lesions.

OBJECTIVE: We aim to investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM). METHODS: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl transfer RNA synthetase antibodies in the patients with DM (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach. RESULTS: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and negative monocytes and myeloid dendritic cells. Notably, patients with DM demonstrated enrichment of complement and interferon-α and γ pathway genes compared with those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and the transforming growth factor-β signaling pathway. CONCLUSION: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathologic differences among IIM subtypes. DM was characterized by complement and interferon-α and γ signaling, whereas ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.

Humans