PCBP1 is associated with rheumatoid arthritis by affecting RNA products of genes involved in immune response in Th1 cells.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent synovitis, in which T helper 1 (Th1) can promote the development of a pro-inflammatory microenvironment. Poly(rC)-binding protein 1 (PCBP1) has been identified as a promising biomarker of RA, while its molecular mechanisms in RA development are unknown. As a canonical RNA binding protein, we propose that PCBP1 could play roles in RA by affecting both expression and alternative splicing levels in Th1 cells. Here, microarray datasets (GSE15573 and GSE23561), including 102 peripheral blood mononuclear cell samples from 39 RA patients and 63 controls, were used to evaluate the PCBP1 expression changes in RA patients. High throughput sequencing data (GSE84702) of iron driven pathogenesis in Th1 cells were downloaded and reanalyzed, including two Pcbp1 deficiency samples and two control samples in Th1 cells. In addition, CLIP-seq data of PCBP1 in Jurkat T cells was also analyzed to investigate the regulatory mechanisms of PCBP1. We found PCBP1 were down-regulated in RA specimens compared with control. The result of differentially expressed genes (DEGs) showed that Pcbp1 silencing in Th1 cells affected the expression of genes involved in immune response pathway. Alternative splicing analysis also revealed that PCBP1-regulated alternative splicing genes (RASGs) were enriched in TNF-a/NF-κB signaling pathway, T cell activation, T cell differentiation and T cell differentiation associated immune response pathways, which were highly associated with RA. DEGs and RASGs by Pcbp1 deficiency in mice were validated in PBMCs specimens of RA patients by RT-qPCR. Investigation of the CLIP-seq data revealed PCBP1 preferred to bind to 3'UTR and intron regions. PCBP1-bound genes were also significantly associated with RASGs, identifying 102 overlapped genes of these two gene sets. These genes were significantly enriched in several immune response related pathways, including myeloid cell differentiation and positive regulation of NF-κB transcription factor activity. Two RA-related genes, PML and IRAK1, were screened from the above immune related pathways. These results together support our hypothesis that PCBP1 can regulate the expression of genes involved in immune response pathway, and can bind to and regulate the alternative splicing of immune response related genes in immune T cells, and ultimately participate in the molecular mechanism of RA, providing new research ideas and directions for clinical diagnosis and treatment.

Meta-analysis of the correlation between PTPN22 gene polymorphisms and susceptibility to systemic lupus erythematosus.

In this meta-analysis of the association between PTPN22 gene polymorphisms and susceptibility to systemic lupus erythematosus, 4 case-control studies, including one from China, were included. The studies included 1864 participants: 772 cases and 1092 controls. The meta-analysis showed that the 1858C/T polymorphism of the PTPN22 gene is correlated with systemic lupus erythematosus susceptibility, when assessed by distribution characteristics such as nationality, race, and region. A large sample size from the Chinese population is required for a further prospective study before causality can be established.

Correlation between single nucleotide polymorphism of rs3811047 in IL-1 F7 gene and rheumatoid arthritis susceptibility among Han population in central plains of China.

OBJECTIVE: To discuss the association between single nucleotide polymorphism (SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis (RA) susceptibility among the Han population in central plains of China. METHODS: A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects. The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique. And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility. RESULTS: The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27% and 17.68%, respectively, and that of G allele in two groups was 83.73% and 82.32%, respectively. The difference between two groups wasn't statistical significant (P >0.05). The frequency of genotype AA, AG and GG in RA group was 2.19%, 27.84% and 69.97%, respectively, while that in control group was 2.94%, 29.78% and 67.28%, respectively. The difference of distribution of three genotypes was not statistically significant (P >0.05). RA patients with A allele were better than those without A allele in joint swelling index, rest pain, HAQ scoring and blood sedimentation. There was significant difference between two groups in above indexes (P<0.05/P<0.01). CONCLUSIONS: No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed. However, A allele of rs3811047 has certain influence on the condition of RA patients.