miR-210 expression in PBMCs from patients with systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: In hypoxic conditions, miRNA-210 plays an important role in regulating the expression of hypoxia-inducing factor-1α (HIF-1α) and the differentiation of T helper 17 (Th17) cells, and this may be involved in the development and function of the immune system. AIMS: This study was to investigate the miR-210 expression levels in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and its association with the clinical and laboratory features of both diseases. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect miR-210 expression levels in PBMCs from 35 patients with SLE, 38 patients with RA, and 35 healthy controls. RESULTS: Compared with the healthy controls, the miR-210 expression levels were significantly increased in patients with SLE (P = 0.001) and there was increased significantly expression of miR-210 in SLE with pleuritis (Z = -2.345, P = 0.019) and anti-SSB/La-positive group (Z = -2.076, P = 0.038). However, we have not found the significant correlation between the miR-210 levels and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (r s = 0.091, P = 0.602). Although, no significant difference between miR-210 levels in RA patients and those in healthy controls was found (Z = -1.226, P = 0. 220). There was a significant decreased expression of miR-210 in active RA patients than inactive RA patients (Z = -4.011, P < 0.001). CONCLUSIONS: The dysregulation of miR-210 levels in SLE and RA patients suggests that miR-210 might play an important role in the pathogenesis of these diseases.

Association between IRAK1 rs3027898 and miRNA-499 rs3746444 polymorphisms and rheumatoid arthritis : A case control study and meta-analysis.

BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. MATERIAL AND METHODS: A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies. RESULTS: This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093-1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130-1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096-1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations. CONCLUSION: The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.

Elevated plasma interleukin-37 levels in systemic lupus erythematosus patients.

This study aims to evaluate the plasma interleukin (IL)-37 levels in systemic lupus erythematosus (SLE) patients, as well as its association with major clinical and laboratory features. Ninety consecutively selected SLE patients and 78 community-based healthy controls were recruited. Plasma IL-37 levels were detected by enzyme-linked immunosorbent assay (ELISA). The major clinical and laboratory data of SLE patients were also recorded. The results showed that IL-37 level was significantly higher in the plasma of patients with SLE compared with controls (p = 0.028). The correlation of plasma IL-37 levels with major clinical and laboratory data of SLE patients was also analyzed, and the results showed that anti-Sm and anti-RNP were negatively associated with plasma IL-37 levels of SLE patients, while C3 was positively associated with plasma IL-37 levels of SLE patients. No significant associations of IL-37 with other clinical and laboratory parameters were observed (all p > 0.05). In conclusion, elevated plasma IL-37 level and its associations with anti-Sm, anti-RNP and C3 in SLE patients suggest that IL-37 may be implicated in this disease.

Serum levels of cytokines in systemic lupus erythematosus : Association study in a Chinese population.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. The clear pathogenesis of SLE has not been fully elucidated. Cytokine-mediated immunity has been showed to be involved in the pathogenesis of SLE. OBJECTIVES: The aim of this study was to investigate serum levels of cytokines (IL-19, IL-24, IL-26, IL-31, IL-32, IL-36) in SLE patients, in comparison with normal controls in a Chinese population. MATERIALS AND METHODS: A total of 65 patients with SLE and 65 healthy volunteers were recruited for the current study. All serum levels of cytokines were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not significantly different from the normal controls (all p > 0.05). CONCLUSION: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not markedly different from the normal controls. However, functional research should be discussed in future studies to elucidate the roles of these cytokines in SLE.

Sex-specific differences in the relationship between the single-nucleotide polymorphism rs2298804 of FCER1A and the susceptibility to systemic lupus erythematosus in a Chinese Han population.

BACKGROUND: IgE plays a important role in systemic lupus erythematosus (SLE). A recent study identified the high-affinity IgE receptor α-chain (FcεRIα) gene FCER1A as a susceptibility locus influencing total serum IgE levels. AIM: To investigate whether the single-nucleotide polymorphism (SNP) rs2298804 (251 A>G) of FCER1A is associated with SLE and its clinical characteristics in a Chinese Han population. METHODS: This case-control study enrolled 948 patients with SLE and 976 healthy controls. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. rs2298804 was genotyped using real-time fluorescence quantitative PCR. RESULTS: Compared with the healthy controls, patients with SLE had much lower frequencies of the AG genotype (OR = 0.26; 95% CI 0.194-0.374; P << 0.001) and G allele (OR = 0.45; 95% CI 0.36-0.55; P << 0.001). We also found a stronger association of the FCER1A exon SNP, rs2298804 (A/G), in females (OR = 0.42; 95%CI 0.34-0.53; P << 0.001) compared with males (OR = 0.52; 95% CI 0.28-0.97; P < 0.04). G-allele carriers are less likely to develop SLE than A-allele carriers. Although we did not find any significant correlation between the rs2298804 and the incidence of lupus nephritis, rs2298804 seemed to protect against proteinunia, fever and hypocomplementaemia in patients with SLE, but appeared to be a risk factor for photosensitivity and vasculitis. CONCLUSIONS: We found that rs2298804 seemed to have a protective effect against SLE in Chinese patients, especially women. It also protected against proteinunia, fever and hypocomplementaemia, but was a risk factor for photosensitivity and vasculitis.

MicroRNA-101, mitogen-activated protein kinases and mitogen-activated protein kinases phosphatase-1 in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the prototype of human autoimmune disease in which various inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6 and interferon (IFN) play crucial pathogenic roles. The production of these cytokines is responsible for the mitogen-activated protein kinases (MAPKs), which can also generate mitogen-activated protein kinases phosphatases (MKPs). MKP-1, a prototypical member of the MKP family that can influence outcomes of autoimmune diseases and reduce the inflammatory cytokines by dephosphorylation of p38 and JNK MAPK, plays a critical role in the expression of inflammatory mediators at transcriptional and post-transcriptional levels. MicroRNA-101 (miR) is a small non-coding RNA that regulates the MAPK response by targeting MKP-1 mRNA 3'-UTR, and affects the secretion of the downstream inflammatory cytokines. However, the interaction among the above three in the pathogenesis of SLE has not previously been reported. This review discusses the current understanding of the role of the MAPK/MKP/miR-101 axis in regulating immune responses and the pathogenesis of SLE to provide new ideas for clinical treatment of SLE.

Lack of association of interleukin-18 gene promoter -607 A/C polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

OBJECTIVE: Published data on the association between interleukin (IL)-18 gene promoter -607 A/C polymorphism and autoimmune diseases risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: A total of 17 studies, including six studies on type 1 diabetes (T1D), four on rheumatoid arthritis (RA), five on systemic lupus erythematosus (SLE), three on Crohn's Disease (CD) and three on ulcerative colitis (UC), were available for the meta-analysis. Meta-analysis was performed for genotypes A/A (recessive effect), genotypes A/A + A/C (dominant effect), and A allele in fixed or random-effects models. RESULTS: Overall, no significantly elevated autoimmune diseases risk was found in all genetic models when all studies were pooled into the meta-analysis. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for A-allele were T1D (OR = 0.938, 95% CI = 0.757-1.162), RA (OR = 0.759, 95% CI = 0.540-1.067), SLE (OR = 0.858, 95% CI = 0.609-1.208), CD (OR = 1.159, 95% CI = 0.975-1.379) and UC (OR = 1.170, 95% CI = 0.977-1.402), respectively. In the subgroup analysis by ethnicity, there was still no significant association detected in all genetic models. CONCLUSIONS: To date, there is still not enough evidence to indicate the association of IL-18 gene promoter -607 A/C polymorphism and the development of autoimmune diseases.

Ets-1: a new player in the pathogenesis of systemic lupus erythematosus?

v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) (Ets-1) is a member of the Ets family of transcription factors that share a unique Ets DNA binding domain. They control a wide variety of cellular processes including cell proliferation and differentiation. Recently, two genome-wide association studies in systemic lupus erythematosus (SLE) independently identified genetic variants in Ets-1 associated with SLE. Interestingly, previous studies have found that Ets-1-deficient mice develop lupus-like disease characterized by high titers of IgM and IgG autoantibodies, immune complex-mediated glomerulonephritis, and local activation of complement. In addition, Ets-1 is also involved in many cellular abnormalities that are known to participate in SLE pathogenesis, such as its role in negative regulation of Th17 cell and B cell differentiation. All these findings suggest that Ets-1 may play an important role in the pathogenesis of SLE. This article will focus on current understanding of the role of Ets-1 in the physiological and pathological functions associated with SLE. It is the intention of the article to provide insights which may assist in the development of Ets-1 based approaches for the treatment of SLE.