An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Abstract

Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that affected significantly spinal cord, nevertheless, the pathogenesis pathway. This study aimed to employ high throughput metaanalysis to find major genes involved in the pathogenesis of HAM/TSP. High-throughput statistical analyses identified 385, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. STRING and further network analyses highlighted 32, 29, and 13 hub genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. Biological network analyses indicated the involvement of hub genes in the HAM/TSP group in many vital pathways like apoptosis and immune pathways. Moreover, the meta-analysis results disclosed three major genes including STAT1, TAP1, and PSMB8 which have function role in HAM/TSP progression. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P=0.01 and P=0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P=0. 04 and P=0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P=0.008 and P=0.02, respectively). No significant difference was found among three groups in terms of percentage of T helper and cytotoxic T lymphocytes (P= 0.55 and P=0.12). Our results confirm that STAT1, TAP1, and PSMB8 are three important genes which their expressions levels were changed in three different groups. These proteins in association with other proteins can involve in the immune and apoptosis pathways.

Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis

“…Dendritic cells are also known for their robust antiviral signaling with proinflammatory cytokines. Nevertheless, production of type 1 interferons by DCs provide modest benefit to patients possibly due to interference of tax with the intracellular antiviral signaling cascade (Bangham, 2018), reduced interferon secretion in the majority of DCs (Moles et al, 2019) and reduction in expression and phosphorylation of STAT1 in PBMCs (Mozhgani et al, 2019). Recently, the visualization of DCs in choroid plexus of normal rats has led to the hypothesis that DC access to CNS antigens may play an important role in inflammatory and immune-mediated disorders of CNS (McMenamin, 1999).…”

Exploration of mRNAs and miRNA classifiers for various ATLL cancer subtypes using machine learning

“…Several studies explored the possible pathogenesis mechanisms of the HTLV-1 infection in ACs toward ATLL and/or HAM/TSP [2,[11][12][13][14][15]. However, some of them considered ATLL disregarding the subtypes.…”