We investigated the frequency of IFNG gene intron (+874) polymorphism, previously reported to be associated with IFNG production, in SLE patients compared to a control group.
Previous studies have revealed the elevated serum levels of High-mobility group box-1(HMGB1) and the interferon-γ (IFN-γ)-induced proliferation of renal mesangial cells in patients or experimental animals with systemic lupus erythematosus (SLE).
This meta-analysis indicates that the IFN-γ+874 T/A polymorphism may play a significant role in modifying the risk of autoimmune diseases in Caucasian, Latin American, and Middle Eastern subjects, and in particular shows that the IFN-γ+874 T/A polymorphism is associated with increased genetic susceptibility to idiopathic thrombocytopenic purpura and SLE.
Gene expressions of T-bet, GATA-3, interferon-gamma (IFN-gamma), and interleukin 4 (IL-4) in peripheral blood mononuclear cells, and plasma concentrations of the Th1/Th2 cytokines IFN-gamma, IL-18, and IL-4, were assayed in 80 patients with SLE and 40 sex and age matched healthy subjects by real-time quantitative polymerase chain reaction and ELISA.
Therefore, the imbalance of IFN-gamma/IL-4 producing CD4+ T cells was due to the decrease in IL-4 producing CD4+ T cells and may play an important pathogenic role in active SLE.
Our results showed increased percentage of autophagy in IFN-γ<sup>+</sup> T cells from patients with SLE and healthy controls ([8.07 ± 2.72]% vs. [3.76 ± 1.67]%, t = 5.184, P < 0.001), but not in IL-4<sup>+</sup> T cells or IL-17<sup>+</sup> T cells (P > 0.05) as compared to healthy donors.
However, the transcript levels of IL-10 and TNF-α as well as the protein and transcript levels of IFN-γ were comparable between SLE and normal control groups.
Multiplex Luminex technology results showed a normal induction of five quantified cytokines (interferon γ, interleukin(IL)12, IL17, IL10, and tumor necrosis factor α) in SLE patients compared to HCs upon stimulation with CMVpp52 and HHV6p41.
IL-18 and IFN-γ have also been implicated in the onset of different types of immune-mediate inflammatory conditions such as Type 1 Diabetes (T1D), Celiac disease (CD), rheumatoid arthritis (RA), obesity and systemic lupus erythematosus (SLE).
Circulating CpG motif-containing DNA fragments in SLE increased mRNA encoding IL-12 and IFN-gamma, which in turn increased HLA-DR and ICAM-1 on monocytes, resulting in MNC proliferation.
We show that elevated levels of IFNγ in SLE patients correlate with expansion of the T-bet expressing IgD<sup>neg</sup>CD27<sup>neg</sup>CD11c<sup>+</sup>CXCR5<sup>neg</sup> (DN2) pre-antibody secreting cell (pre-ASC) subset.
Among the SLE patient groups, there was a close correlation between IFNgamma expression and the overall SLE Disease Activity Index (SLEDAI) score (Spearman's r = 0.590, P < 0.001) and the SLEDAI renal score (r = 0.642, P < 0.001).
The relative expressions of T-bet/GATA-3 and IFN-gamma/IL-4 correlated with lupus disease activity (r = 0.229, p = 0.042; r = 0.231, p = 0.040, respectively).