Single-cell RNA transcriptomics divulged altered gene expressions in monocytes and HLA variations in decompensated cirrhosis patients with sepsis

Immune dysfunction and systemic inflammation are hallmarks of decompensated liver cirrhosis (DLC), associated with an increased risk of developing sepsis. Rapid immune degradation is poorly understood in DLC patients; therefore we performed single-cell RNA (scRNA) transcriptomics in DLC patients. Twenty-one DLC patients (all males, 42 ± 7 year) with sepsis (n = 10) and without sepsis (w/o, n = 11) and ten healthy controls PBMCs, were analysed for scRNA transcriptomics using the BD Rhapsody. Cell clustering and cell types were determined using gene expression data and validation of specific genes was done by qRT-PCR. Retrospectively analyzed proteomics data from same patients was used for RNA-Protein interactions. Ten clusters and 7 cell types were detected, with high heterogeneity in the monocyte cluster in DLC patients. All DLC patients irrespective of sepsis showed down regulation of O6-methylguanine-DNA methyltransferase (MGMT) mediated DNA damage reversal, mitochondrial transcription termination, and melanin biosynthesis, with upregulated lactose synthesis, hydroxycarboxylic acid, FGFR1b and FGFR1c receptors. DLC-sepsis showed down regulation of NF-kβ, TNF-α, and IL-17 signaling in classical monocytes compared to w/o sepsis. Serotonin and DNA repair genes were significantly increased in DLC sepsis (P < 0.05). In addition to HLA-DR, HLA-A, HLA-B, and HLA-DQA1 were also decreased but HLA-DRB1, HLA-C, HLAE, HLA-DRA, and HLA-DQA2 were raised in sepsis. RNA-protein interaction revealed the down regulation of PROS1, CDC42, CD62L, FCGR3B, CX3CR1, Rpl31 genes in sepsis. Chances of sepsis increased in DLC patients due to monocytic defects in genes and signaling pathways. These markers further can be explored for diagnostic purposes and early detection of sepsis.