MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an aberrant activation of immune cells partly due to the dysfunction of cytokines such as type I interferons (IFNs). Long non-coding RNA MALAT1 has been found to play a pathogenic role in SLE; however, the underlying mechanisms are still poorly understood. Bioinformatics analysis showed the up-regulation of type I IFN downstream effectors OAS2, OAS3, and OASL (OAS-like) in CD4+ T cells, CD19+ B cells, and CD33+ myeloid cells in patients with active SLE compared to healthy participants. In this study, peripheral blood mononuclear cells (PBMCs), CD19+ B, and CD4+ T cells were isolated from active SLE patients and healthy participants. PCR was performed to quantify MALAT1, OAS2, OAS3, and OASL expression in immune cells. MALAT1, OAS2, OAS3, and OASL were knocked down in CD4+ T cells to investigate the regulatory effect of MALAT1 on the effectors and their involvement in type I IFNs-mediated inflammation. Results showed higher OAS2, OAS3, and OASL expression in active SLE patients. MALAT1 expression was positively correlated to OAS2, OAS3, and OASL expression in CD19+ B or CD4+ T cells. MALAT1 knockdown decreased OAS2, OAS3, and OASL expression. Treatment with IFN-α-2a increased the expression of TNF-α, IL-1β, and IFN-α in CD4+ T cells. However, knockdown of MALAT1, OAS2, OAS3, and OASL alone inhibited the effect of IFN-α-2a on TNF-α and IL-1β. This study suggested the involvement of MALAT1 in type I IFNs-mediated SLE by up-regulating OAS2, OAS3, and OASL.

Polymorphism of OAS2 rs739901 C/A Involves the Susceptibility to EV71 Infection in Chinese Children / 华中科技大学学报（医学）（英德文版）

This study aimed to assess the relationship of OAS2 rs739901 5'-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 (EV71) infection.We investigated 294 hand-foot-mouth disease (HFMD) Chinese children with EV71 infection (165 mild cases and 129 encephalitis cases).The improved multiplex ligation detection reaction (iMLDR) technique was used to test the genotypes.In EV71-infected patients,the CA genotype distribution (P=0.007),A allele frequency (OR 1.32,95％ CI 1.0-1.7,P=0.034)and CA+AA carriage frequency (P=0.003) of OAS2 rs739901 5'-flanking were obviously elevated as compared with controls,but there were no statistically significant differences between mild cases and encephalitis cases.In EV71-infected patients,the counts of white blood cells (P=0.034) and blood glucose concentrations (P=0.042) were raised in A carriers (CA+AA).Among different genotypes of encephalitis cases,the contents of cerebrospinal fluid (CSF) showed no significant differences.IFN-γ levels in EV71-infected patients were higher than those in controls (mild group vs.control group,P＜0.01;encephalitis group vs.control group,P＜0.001).In encephalitis cases,IFN-γ levels were reduced (P＜0.05) in A carriers compared to CC genotype,however,there were no significant differences between genotypes CA and AA (P=0.226).These findings suggest that OAS2 rs739901 5'-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection,and A allele might be a risk factor of the susceptibility to EV-71 infection.

Polymorphism of OAS2 rs739901 C/A Involves the Susceptibility to EV71 Infection in Chinese Children / 华中科技大学学报（医学）（英德文版）

This study aimed to assess the relationship of OAS2 rs739901 5'-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 (EV71) infection.We investigated 294 hand-foot-mouth disease (HFMD) Chinese children with EV71 infection (165 mild cases and 129 encephalitis cases).The improved multiplex ligation detection reaction (iMLDR) technique was used to test the genotypes.In EV71-infected patients,the CA genotype distribution (P=0.007),A allele frequency (OR 1.32,95％ CI 1.0-1.7,P=0.034)and CA+AA carriage frequency (P=0.003) of OAS2 rs739901 5'-flanking were obviously elevated as compared with controls,but there were no statistically significant differences between mild cases and encephalitis cases.In EV71-infected patients,the counts of white blood cells (P=0.034) and blood glucose concentrations (P=0.042) were raised in A carriers (CA+AA).Among different genotypes of encephalitis cases,the contents of cerebrospinal fluid (CSF) showed no significant differences.IFN-γ levels in EV71-infected patients were higher than those in controls (mild group vs.control group,P＜0.01;encephalitis group vs.control group,P＜0.001).In encephalitis cases,IFN-γ levels were reduced (P＜0.05) in A carriers compared to CC genotype,however,there were no significant differences between genotypes CA and AA (P=0.226).These findings suggest that OAS2 rs739901 5'-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection,and A allele might be a risk factor of the susceptibility to EV-71 infection.