Association of interleukin-6 and interleukin-10 expression, gene polymorphisms, and Takayasu arteritis in a Chinese Han population

Abstract

Takayasu arteritis (TA) is a chronic inflammatory disease. Interleukin (IL)-6 and IL-10 are important cytokines involved in the immune response of TA in some ethnicities. We investigated whether the single-nucleotide polymorphism (SNP) of IL-6 and IL-10 genes and their expressions were associated with TA in a Chinese Han population. One hundred eighty-four TA patients and 235 healthy controls (HC) were recruited. DNA and RNA were extracted from peripheral blood cells. Genotyping of IL-6 and -10 was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR). The mRNA levels of IL-6 and IL-10 were semi-quantified using reverse transcription polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction (real-time PCR). Plasma levels of them were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-6 in active phase of TA were higher than those in stable phase (p = 0.015); the IL-10 in active phase was lower compared with stable phase (p = 0.046). Plasma levels of IL-6 in TA were higher than those in HC (p = 0.024). Plasma levels of IL-10 showed no difference between the two groups (p = 0.264). Plasma levels of IL-6 in active phase were increased than those in stable phase (p = 0.043) while those of IL-10 were decreased in active phase (p = 0.041). We found no significant differences between TA and HC in the frequency of any of the variations in the SNPs of IL-6 and IL-10 genes. The expression levels of both cytokines were associated with the disease status, indicating that they may serve as potential biomarkers for monitoring disease activity.

Biomarker Changes and Molecular Signatures Associated with Takayasu Arteritis Following Treatment with Glucocorticoids and Tofacitinib

“…It was significantly reduced in active patients compared with stable patients, and higher IL-10 levels was correlated with a long-term remission of TAK. 26 , 27 In the present study, there was no significant difference in serum IL-10 levels between TAK patients at baseline and healthy controls. However, after 6 months of GCs and TOF treatment, IL-10 was significantly increased in TAK patients, indicating that GCs and TOF could enhance the anti-inflammatory responses.…”

Systemic review and meta‐analysis of the association between interleukin‐10 and Takayasu arteritis

“…Two studies reported rs1800871 polymorphism and TAK, 14,15 while no significant relationship was found, which were T vs t: 1.22 (95% CI: 0.90, 1.64, I 2 = 0%); TT vs tt: 1.48 (95% CI: 0.78, 2.80, I 2 = 0%); Tt vs tt: 1.44 (0.89, 2.35, I 2 = 0%); TT + Tt vs tt: 1.44 (95% CI: 0.90, 2.29, I 2 = 0%); and TT vs TT + Tt: 1.16 (95% CI: 0.67, 2.01, I 2 = 0%) (all P > 0.05, Figure 3). Three reported rs1800872 polymorphism, 5,14,15 yet no significant relationship was found, which were T vs t: 0.97 (95% CI: 0.79, 1.20, I 2 = 0%); TT vs tt: 0.94 (95% CI: 0.59, 1.50, I 2 = 0%); Tt vs tt: 1.22 (95% CI: 0.83, 1.79, I 2 = 0%); TT + Tt vs tt: 1.39 (95% CI: 0.95, 2.03, I 2 = 55%); and TT vs TT + Tt: 0.86 (95% CI: 0.62, 1.19, I 2 = 0%) (all P > 0.05, Figure 4). Two reported rs1800896 polymorphism, 14,15 also, no significant relationship was found, which were T vs t: 1.11 (95% CI: 0.77, 1.58, I 2 = 34%); TT vs tt: 1.15 (95% CI: 0.40, 3.28, I 2 = 0%); Tt vs tt: 0.99 (95% CI: 0.34, 2.90, I 2 = 0%); TT + Tt vs tt: 1.11 (95% CI: 0.39, 3.13, I 2 = 0%); and TT vs TT + Tt: 1.11 (95% CI: 0.72, 1.70, I 2 = 56%) (all P > 0.05, Figure 5).…”

“…After this preliminary screening, 17 studies were selected through screening the full text. According to the inclusion and exclusion criteria, 7 studies were eventually selected for the meta-analysis 5,[12][13][14][15][16][17] (Figure 1).…”

“…Also, it can enhance the immune responses 4 . IL‐10 is an important cytokine involved in TAK immune response in some ethnicities 5 . Some studies have shown that the levels of IL‐10 in TAK the active phase were lower than that in the stable phase 5 .…”

Using the co-expression network of T cell-activation-related genes to assess the disease activity in Takayasu’s arteritis patients

“…Secondly, we found that when comparing the active TAK patients to the inactive TAK patients, although there were increased mRNA levels of TCR, CD28, GATA3, RORC, and FOXP3, which indicate that T cells were involved in the disease activity of TAK, these mRNA levels of many immune checkpoints were not increased, such as CTLA4, PD-1, LAG3, TIGIT, and TIM3. We speculate that it might be related to the attenuated secretion of IL-10 in PBMCs of TAK patients [ 32 , 41 – 43 ]. Notably, although these immune checkpoints were not increased in active stage than in inactive stage, the emerging gene co-expression revealed the activation of these immune checkpoints in active TAK stage, which suggests that gene co-expression network might more accurately reflect the activation of T cells than the gene expression levels in TAK.…”