ABSTRACT: While VLS is a serious skin disease affecting women in an annoying, embarrassing, and prolonged way worldwide, its pathogenesis and molecular characteristics are still unexploreed. Previous studies have suggested the correlation between inflammation or microRNA and VLS, but the lack of comprehensive understanding on its mechanism prevents the development of precision medicine for it. For a long time, VLS has been speculated as an autoimmune disease (Tran, Tan et al., 2019). This hypothesis was derived from several clinical observations: (1) VLS is frequently observed in women with an autoimmune diseases called Turner Syndrome (Chakhtoura, Vigoureux et al., 2014) ; (2) Many VLS patients also develop various autoimmune diseases (Kreuter, Kryvosheyeva et al., 2013, Song, Xiaoli et al., 2018) ; (3) VLS patients may also have higher frequency of certain HLA antigens, though few immunological consequence has been studied (Sideri, Rognoni et al., 1988). Microarray assay found upregulation of Th1, microRNA-155 and relative transcripts using VLS and healthy donors biopsies (Ren, Zhao et al., 2018, Terlou, Santegoets et al., 2012). However, the person-to-person genotype variation can hardly eliminate without using normal tissues from the same patient; and the PCR-based measurement of transcriptome of microarray limited the data interpretation and assumption validation. In this article, we performed multi-omics analyses on VLS paired-samples from the same patients as well as the normal ones from healthy donors. RNA-seq analysis revealed VLS patients are suffering from abnormally high inflammation with impressive anti-virus features. In-depth analysis of their transcriptome identified a remarkable enrichment of HCV poly U/UC sequence in VLS transcriptome, which might contribute to the onset of VLS. Multi-omics results indicated various inflammation-induced metabolic disorders in VLS samples, which might serve as therapeutic targets for precision medicine.
