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The diagnostic accuracy of cerebrospinal fluid (CSF) anti-human T-cell leukemia virus type I (HTLV-1) antibody testing for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) remains unclear. Therefore, we measured the anti-HTLV-1 antibody levels in CSF using various test kits, evaluated the stability of CSF antibodies, and performed a correlation analysis using the particle agglutination (PA) method, as well as a receiver operating characteristic (ROC) analysis between patients with HAM and carriers. The CSF anti-HTLV-1 antibody levels were influenced by freeze–thaw cycles but remained stable when the CSF was refrigerated at 4 °C for up to 48 h. Measurements from 92 patients (69 patients with HAM and 23 carriers) demonstrated a strong correlation (r > 0.9) with the PA method across all six quantifiable test kits. All six test kits, along with CSF neopterin and CXCL10, exhibited areas under the ROC curve greater than 0.9, indicating a high diagnostic performance for HAM. Among these, five test kits, Lumipulse and Lumipulse Presto HTLV-I/II, HISCL-UD (a kit under development), HTLV-Abbott, and Elecsys HTLV-I/II, established a cutoff with 100% sensitivity and maximum specificity, achieving a sensitivity of 100% and a specificity ranging from 43.5% to 56.5%. This cutoff value, in combination with clinical findings, will aid in the accurate diagnosis of HAM. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (cHL) is characterized by multinucleated cells called Reed‐Sternberg (RS) cells and genetic complexity. Although CD30 also characterizes cHL cells, its biological roles are not fully understood. In this report, we examined the link between CD30 and these characteristics of cHL cells. CD30 stimulation increased multinucleated cells resembling RS cells. We found chromatin bridges, a cause of mitotic errors, among the nuclei of multinucleated cells. CD30 stimulation induced DNA double‐strand breaks (DSBs) and chromosomal imbalances. RNA sequencing showed significant changes in the gene expression by CD30 stimulation. We found that CD30 stimulation increased intracellular reactive oxygen species (ROS), which induced DSBs and multinucleated cells with chromatin bridges. The PI3K pathway was responsible for CD30‐mediated generation of multinucleated cells by ROS. These results suggest that CD30 involves generation of RS cell‐like multinucleated cells and chromosomal instability through induction of DSBs by ROS, which subsequently induces chromatin bridges and mitotic error. The results link CD30 not only to the morphological features of cHL cells, but also to the genetic complexity, both of which are characteristic of cHL cells. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion This study aimed to validate the clinical utility of cerebrospinal fluid (CSF) CXCL10 measurements in HTLV‐1‐associated myelopathy (HAM) using a CXCL10 ELISA “Cosmic” kit, a more widely applicable method than cytometric bead array (CBA).CSF CXCL10 levels were measured in 165 samples from 111 patients with HAM and 18 controls using a CXCL10 ELISA “Cosmic” kit. We assessed the following: (1) CSF CXCL10 concentrations by HAM activity level (high, moderate, and low) versus controls; (2) correlation with CBA; (3) cutoff values, sensitivity, and specificity for differentiating among HAM activity levels; (4) changes in HAM activity after steroid therapy; and (5) relationship between HAM activity and prognosis in patients undergoing steroid therapy. A correlation coefficient of ≥0.9 with CBA was the primary endpoint.The median CSF CXCL10 levels in the high, moderate, low, and control groups were 4016.0, 841.0, 112.8, and 102.5 pg/mL, respectively. The ELISA findings were highly correlated with the CBA findings (r = 0.99). Cutoff values were set at 2500 pg/mL (sensitivity, 93.3%; specificity, 100%) to distinguish between high and moderate activity and 180 pg/mL (sensitivity, 81.8%; specificity, 100%) for low to moderate activity comparable to CBA. The new cutoffs enabled the detection of HAM activity changes and prediction of motor disability progression under steroid therapy.CXCL10 ELISA “Cosmic” kit findings were strongly correlated with CBA findings, meeting the primary endpoint and demonstrating comparable sensitivity and specificity for distinguishing HAM activity. This product shows a promising ability to determine the therapeutic strategy. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus type 1 (HTLV-1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T-cell leukemia-lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV-1-infected individuals using RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq). The infected cells showed significant changes in gene expression patterns from the polyclonal stage and before ATL onset while demonstrating similarities to tumor-forming ATL cells. These similarities were a result of large-scale open chromatin changes, supporting the independent early formation of epigenomic aberrations as an underlying mechanism for later clonal propagation. This study also demonstrated that HTLV-1 Tax directly affects the host chromatin structure, thereby developing fundamental epigenomic characteristics. Several Tax target genes, including the RASGRP3-ERK pathway, were recognized, indicating an impact on signaling pathways. This genome-wide variability in chromatin structural property is a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms. In addition, it has crucial implications for better understanding the impact of HTLV-1 on the host genome and identifying novel therapeutic targets., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)