Table 3.
Characteristics of the top 10 genes that distinguish JIA patients and controls
| Gene | Bonferroni corrected P-value | log-2 fold change | Function of gene product |
|---|---|---|---|
| CXCL8 (IL8) | 4.12 × 10−10 | 6.11 | CXCL8 mediates the activation and migration of neutrophils into tissue from peripheral blood. IL-6 treatment of PBMCs or RA synoviocytes leads to increased CXCL8 production [20] |
| SOCS3 | 4.21 × 10−10 | 2.98 | Suppressor of cytokine signalling 3 (SOCS3) inhibits multiple pathways including IL-6 and NF-κB signalling. Expression induced by various cytokines, including IL-6, IL-10 and IFN-γ. Protein binds to and inhibits JAK kinase. SOCS3 has been shown to limit severe joint inflammation in a mouse model of arthritis. SOCS3 is a major negative regulator of STAT3 [21, 22] |
| G0S2 | 5.59 × 10−10 | 5.56 | G0/G1 SWITCH GENE 2 is highly conserved between vertebrates and was identified during cell cycle progression. Roles in lipid metabolism, cell proliferation. Expression of G0S2 was significantly upregulated in primary human fibroblasts treated with the proapoptotic factor TNF-α [23, 24] |
| JUNB | 1.49 × 10−8 | 1.82 | JunB is a member of the activator protein-1 family and regulates T cell function. JunB activates several cytokine genes including IL-2, IL-4 and IL-10. TNF-α and IL-17 induce nuclear translocation of JunB in RA synoviocytes [25, 26] |
| OSM | 1.62 × 10−7 | 2.55 | Oncostatin M (OSM) is an IL-6 cytokine family member. It contributes to MMP expression and human cartilage destruction. Anti-OSM mAbs have been assessed in phase II clinical trials for RA and suggest a need for an anti-OSM mAb with high affinity for greater efficacy [27] |
| DUSP1 | 4.51 × 10−7 | 2.45 | Dual-specificity phosphatase 1 (DUSP1) inactivates members of the MAPK family and controls mediators of inflammation including TNF. In an arthritis model, Dusp1−/− mice had earlier disease onset and increased disease severity [28] |
| NR4A2 | 2.50 × 10−6 | 3.58 | Orphan nuclear receptor NR4A2 is a key regulator of inflammation. NR4A2 induces synoviocyte proliferation and invasion, and MMP13 transcription [29] |
| MIR22HG | 6.71 × 10−6 | 1.37 | MIR22HG encodes a long ncRNA that is 2699 nucleotides in length. Chemical stressors including cycloheximide have been shown to prolong the decay rate of MIR22HG in human induced pluripotent stem cells [30] |
| AREG | 1.10 × 10−5 | 3.82 | Amphiregulin (AREG) is a growth factor shown to be expressed by several types including activated Th2 cells. AREG enhances Treg suppressive function Treg function at the site of inflammation via EGFR [31] |
| RGS1 | 1.19 × 10−5 | 2.21 | Regulator of G-protein signalling 1 (RGS1) reduces macrophage chemotaxis and dampens chemokine receptor signalling. RGS1 is expressed at low basal levels in healthy PBMCs, with constitutive expression reported to be limited to monocytes. TNF-α and IL-17 have been shown to upregulate RGS1 expression in a monocyte-derived human cell line (U937) [32, 33] |
EGFR: epidermal growth factor receptor; MAPK: mitogen-activated protein kinase; MMP: matrix metalloprotease; ncRNA: non-coding RNA; NF-κB: nuclear factor-κB; PBMC: peripheral blood mononuclear cell; STAT3: signal transducer and activator of transcription 3.