Table 1.
Genes upregulated by dexamethasone in severely ill patients | ||||
---|---|---|---|---|
gene | Full name | Pathways | P-value | |
1 | IFI27 | interferon alpha inducible protein 27 | MAPK Signaling Type I Interferon Signaling |
0.0001 |
2 | TIGIT | T cell immunoreceptor with Ig and ITIM domains |
Immune Exhaustion
T-cell Costimulation |
0.0008 |
3 | IFNB1 | interferon beta 1 | DNA Sensing JAK-STAT Signaling NLR Signaling RNA sensing TNF Signaling Type I Interferon Signaling |
0.0011 |
4 | LAG3 | lymphocyte activating 3 |
Immune Exhaustion
MHC Class II Antigen Presentation T-Cell Costimulation |
0.0012 |
5 | IFITM2 | interferon-induced transmembrane protein 2 | MAPK Signaling Type I Interferon Signaling |
0.0015 |
6 | PDCD1 | programmed cell death 1 |
Immune Exhaustion
T-cell Costimulation TCR Signaling |
0.0017 |
7 | IFNL1 | interferon, lambda 1 | JAK-STAT Signaling Other Interleukin Signaling Type III Interferon Signaling |
0.0024 |
8 | IFI6 | interferon alpha inducible protein 6 | NLR Signaling DNA sensing |
0.0025 |
9 | VCAM1 | vascular cell adhesion molecule 1 | Lymphocyte Trafficking NF-kB Signaling Other Interleukin Signaling Type II Interferon Signaling |
0.0029 |
10 | IFITM3 | interferon-induced transmembrane protein 3 | MAPK Signaling Type I Interferon Signaling |
0.0043 |
11 | IL6 | interleukin 6 | IL-6 Signaling DNA Sensing HIF1A Signaling JAK-STAT Signaling Mononuclear Cell Migration Myeloid Activation NLR Signaling TH17 Differentiation Th2 Differentiation Tissue Stress TNF Signaling |
0.0070 |
12 | RAC2 | Rac family small GTPase 2 | BCR Signaling Lymphocyte Trafficking Myeloid Activation Myeloid Inflammation |
0.0086 |
13 | IFNG | interferon gamma | HIF1A Signaling JAK-STAT Signaling Myeloid Activation Other Interleukin Signaling TCR Signaling TGF-beta Signaling Th1 Differentiation Type II Interferon Signaling |
0.0101 |
14 | IL10RB | interleukin 10 receptor, beta | JAK-STAT Signaling Other Interleukin Signaling Treg Differentiation Type III Interferon Signaling |
0.0116 |
15 | TMPRSS2 | transmembrane serine protease 2 | Virus-Host Interaction | 0.0141 |
16 | IFNA2 | interferon alpha 2 | DNA Sensing JAK-STAT Signaling NLR Signaling RNA Sensing Type I Interferon Signaling |
0.0157 |
17 | BCL3 | BCL3 transcription coactivator | TNF Signaling | 0.0159 |
18 | LITAF | lipopolysaccharide-induced TNF factor | Lysosome | 0.0161 |
19 | IRF7 | interferon regulatory factor 7 | DNA Sensing NLR Signaling RNA Sensing TLR Signaling Type I Interferon Signaling Type II Interferon Signaling |
0.0179 |
20 | ISG15 | ISG15 ubiquitin-like modifier | Interferon Response Genes RNA Sensing Type I Interferon Signaling |
0.0184 |
21 | CTLA4 | cytotoxic T-lymphocyte-associated protein 4 |
Immune Exhaustion
T-cell Costimulation TCR Signaling |
0.0186 |
22 | CD40LG | CD40 ligand |
NF-kB Signaling
T-cell Costimulation TCR Signaling |
0.0194 |
23 | IL18 | interleukin 18 | DNA Sensing IL-1 Signaling Myeloid Activation NLR Signaling |
0.0200 |
24 | TLR3 | toll-like receptor 3 | DNA Sensing Myeloid Activation TLR Signaling |
0.0211 |
25 | ITGB2 | integrin subunit beta 2 | Complement System Lymphocyte Trafficking Myeloid Activation NK Activity Other Interleukin Signaling TLR Signaling |
0.0211 |
26 | CCR5 | C-C motif chemokine receptor 5 |
Chemokine Signaling
Virus-Host Interaction |
0.0257 |
27 | GZMA | granzyme A | Cytotoxicity | 0.0273 |
28 | HLA-C | major histocompatibility complex, class I, C | MHC Class I Antigen Presentation Myeloid Activation Type I Interferon Signaling Type II Interferon Signaling |
0.0286 |
29 | IL18RAP | interleukin 18 receptor accessory protein | IL-1 Signaling Myeloid Activation Oxidative Stress Response |
0.0317 |
30 | CD86 | CD86 molecule |
Immune Exhaustion
Other Interleukin Signaling T-cell Costimulation |
0.0331 |
31 | HCST | hematopoietic cell signal transducer | NK Activity | 0.0344 |
32 | SELENOS | selenoprotein S | Oxidative Stress Response Proteotoxic Stress |
0.0349 |
33 | MAF | MAF bZIP transcription factor | Th2 Differentiation | 0.0355 |
34 | FASLG | Fas ligand (TNF superfamily, member 6) | Apoptosis Cytotoxicity Immune Exhaustion NF-kB Signaling Other Interleukin Signaling |
0.0383 |
35 | IL11RA | interleukin 11 receptor subunit alpha | IL-6 Signaling JAK-STAT Signaling |
0.0399 |
36 | IFI16 | interferon alpha inducible protein 6 | DNA Sensing NLR Signaling |
0.0417 |
37 | CD45R0 | protein tyrosine phosphatase receptor type C | Immune Memory Myeloid Activation TCR Signaling |
0.0508 |
38 | PRDM1 | PR/SET domain 1 | BCR Signaling | 0.0513 |
39 | EOMES | eomesodermin | Immune Exhaustion | 0.0522 |
40 | ZBP1 | Z-DNA binding protein 1 | DNA Sensing | 0.0523 |
1 | IL23A | interleukin 23 subunit alpha | JAK-STAT Signaling Other Interleukin Signaling Th17 differentiation |
0.0041 |
2 | SELL | selectin L | Immune Memory Lymphocyte Trafficking Myeloid Activation |
0.0077 |
3 | TXK | TXK tyrosine kinase | Lymphocyte Trafficking Myeloid inflammation |
0.0082 |
4 | HSP90AB1 | heat shock protein 90 alpha family class B member 1 | Inflammasomes Myeloid Activation NLR Signaling Proteotoxic Stress Th17 Differentiation |
0.0085 |
5 | LEF1 | lymphoid enhancer-binding factor 1 | TCR Signaling | 0.0096 |
6 | CXCR4 | C-X-C motif chemokine receptor 4 |
Chemokine Signaling
Lymphocyte Trafficking Virus-Host Interaction |
0.0102 |
7 | NLRP1 | NLR family pyrin domain containing 1 | Inflammasomes NLR Signaling |
0.0126 |
8 | STRAP | serine/threonine kinase receptor-associated protein | TGF-β Signaling | 0.0134 |
9 | MYC | MYC proto-oncogene, bHLH transcription factor | Other Interleukin Signaling TGF-β Signaling |
0.0159 |
10 | CDK4 | cyclin-dependent kinase 4 | TCR Signaling | 0.0194 |
11 | TNFRSF10B | TNF receptor superfamily member 10b | Apoptosis Cytotoxicity |
0.0262 |
12 | UBA52 | ubiquitin A-52 residue ribosomal protein fusion product 1 | ALPK1 Signaling BCR Signaling DNA Sensing Glycan Sensing Interferon Response Genes NF-κB Signaling RNA Sensing TCR Signaling TGF-β Signaling TLR Signaling TNF Signaling |
0.0275 |
13 | IKBKE | inhibitor of nuclear factor kappa B kinase subunit epsilon | DNA Sensing NLR Signaling RNA Sensing TLR Signaling Type I Interferon Signaling |
0.0313 |
14 | CUL1 | cullin 1 | BCR Signaling Glycan Sensing NF-kB Signaling TCR Signaling TGF-β Signaling TLR Signaling |
0.0520 |
15 | CD28 | CD28 molecule | T-cell Costimulation TCR Signaling |
0.0543 |
16 | C1QBP | complement C1q binding protein | Apoptosis Coagulation |
0.0549 |
Differentially expressed genes were determined by comparing the normalized counts for all genes in NanoString Host Response Panel codeset between the severe COVID-19 (n=3) and severe COVID-19 treated with dexamethasone (n=4) patient groups. Pairwise comparisons were performed using unpaired t-tests. All of the genes that were significantly downregulated or upregulated by dexamethasone are presented in the table, along with their annotations. The pathway annotations for the individual differentially expressed genes are also shown below, and the pathways that are differentially expressed by dexamethasone (shown in Figures 2B, C) and shown in bold.