Decreased T cell expression of H/ACA box small nucleolar RNA 12 promotes lupus pathogenesis in patients with systemic lupus erythematosus

Abstract

Objective To investigate whether the aberrant expression of non-coding RNAs (ncRNAs) in T cells from patients with systemic lupus erythematosus (SLE) could contribute to the pathogenesis of lupus. Methods Expression profiles of RNA transcripts in T cells from three patients with SLE and three controls were analyzed by microarray analysis. Potentially aberrant-expressed ncRNAs were validated using T cell samples from 23 patients with SLE and 17 controls. Transfection studies and microarray analyses were conducted to search for any gene expression that is regulated by specific ncRNAs. Results Initial analysis revealed differential expression of 18 ncRNAs in SLE T cells. After validation, decreased expression of H/ACA box small nucleolar RNA 12 (SNORA12) was confirmed in SLE T cells (0.69-fold, P = 0.007) compared with normal T cells, and its expression level was inversely associated with higher SLE disease activity scores. Jurkat cells transfected with a plasmid encoding SNORA12 showed increased expression of two genes and decreased expression of 15 genes in Jurkat cells. These changes of gene expression were significantly associated with the SLE pathway in the Kyoto Encyclopedia of Genes and Genomes map using microarray analysis. Overexpression of SNORA12 altered the expression of CD69, decreased the expression of histone cluster 1 H4 family member k (HIST1H4K), inhibited the secretion of interferon gamma and the expression of HIST1H4K was increased in SLE T cells. Conclusion Among the ncRNAs, we found that the expression level of SNORA12, which belongs to the family of small nucleolar RNAs, was lower in SLE T cells and affected T cell function. This novel finding suggests that aberrant-expressed snoRNAs lead to dysfunction of T cells and may be involved in the immunopathogenesis of SLE.

Expression of γ-globin genes in β-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin)

“…As far as the second point, we have to point out that the sirolimus content in the blood was found to be variable and low. With regard to variability, the values observed cannot be considered unexpected, since high variability has been found in clinical trials carried out in other diseases [50][51][52]. With regard to overall blood content, it was found lower than expected from published data on other pathologies (Figure 3 and Table IV) [50][51][52].…”

“…With regard to variability, the values observed cannot be considered unexpected, since high variability has been found in clinical trials carried out in other diseases [50][51][52]. With regard to overall blood content, it was found lower than expected from published data on other pathologies (Figure 3 and Table IV) [50][51][52]. For instance, in 90 patients with lymphangioleiomyomatosis the average blood sirolimus level was 7.2 ± 2.6 ng/ml (range 1.5 to 18.6 ng/ml) in the first year of sirolimus treatment under the average dose of 1.27 ± 0.47 mg/day (range 0.5 to 2 mg/day) [51].…”

Epigenetic Alterations in Immune Cells of Systemic Lupus Erythematosus and Therapeutic Implications

“…Decreased expression of H/ACA box small nucleolar RNA 12 (SNORA12) was also found in SLE T cells in a small Taiwanese cohort (n = 23) study [32]. The levels of SNORA12 were inversely associated with higher SLE disease activity scores [32]. Numerous studies have revealed aberrant miRNA patterns in SLE patients and their likely involvement in SLE pathogenesis, including different cellular and molecular pathways.…”

“…Aberrant expression of ncRNAs and many miRNAs are observed in SLE and associated with disease severity [31]. Decreased expression of H/ACA box small nucleolar RNA 12 (SNORA12) was also found in SLE T cells in a small Taiwanese cohort (n = 23) study [32]. The levels of SNORA12 were inversely associated with higher SLE disease activity scores [32].…”

Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis

“…RNA concentration was quantified using a spectrophotometer (NanoDrop 1000, Thermo Fisher Scientific, Waltham, MA, USA). Subsequently, mRNA expression levels were quantified by real-time RT-PCR using a one-step RT-PCR kit (TaKaRa, Shiga, Japan) with an ABI Prism 7500 Fast Real-Time PCR system (Applied Biosystems, Waltham, MA, USA) according to the conditions described previously [42]. The relative expression levels of mRNA were defined by the following equation: (39-threshold cycle (Ct) after adjustment based on the expression of 18S ribosomal RNA).…”