ABSTRACT
We determined the expression of Integrin alpha L chain (ITGAL), Perforin 1 (PRF1), and CD70 and studied the associations with laboratory and clinical parameters. CD4+ T cells were isolated from 35 SLE patients and 30 healthy controls. The transcript levels of ITGAL, PRF1, and CD70 were quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). The SLE patients had significantly elevated transcript levels of ITGAL (18.61±22.17 vs. 7.33±9.17, p=0.042), PRF1 (21.67±26.34 vs. 10.67±11.65, p=0.039), and CD70 (1.45±1.63 vs. 0.67± 0.28, p=0.011). Patients with anti-microsomal and/or anti-thyroglobulin antibodies showed high levels of ITGAL (33.41±30.14 vs. 13.58±16.43, p=0.044; and 34.01±27.66 vs. 11.90±16.17, p=0.007, respectively). No association was seen either for the typical antibodies of SLE or for the disease activity. Although ITGAL, PRF1, and CD70 are overexpressed in SLE CD4+ T cells, their expression is not linked to the typical clinical and serological parameters associated with the disease. The role that ITGAL may play in autoimmune thyroiditis deserves further investigation.
Subject(s)
CD11a Antigen/genetics , CD27 Ligand/genetics , CD4-Positive T-Lymphocytes/immunology , Lupus Erythematosus, Systemic/immunology , Pore Forming Cytotoxic Proteins/genetics , Adult , Aged , Biomarkers/blood , Case-Control Studies , Cells, Cultured , Female , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Male , Middle Aged , Perforin , Predictive Value of Tests , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Serologic Tests , Up-Regulation , Young AdultABSTRACT
OBJECTIVES: We determined the expression of ITGAL, PRF1, KIR2DL4, CD70, and CD40LG in patients with SLE and performed correlations with the global DNA methylation status and the levels of three DNA methylation enzymes and two methyl CpG-binding domain (MBD) proteins. PATIENTS AND METHODS: CD4(+) T cells were isolated from 35 SLE patients and 30 healthy controls. DNA deoxymethylcytosine content was measured by an enzyme-linked immunosorbent assay (ELISA). Transcript levels of ITGAL, PRF1, KIR2DL4, CD70, CD40LG, DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4 were quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: SLE patients had significantly elevated transcript levels of ITGAL (18.61±22.17 vs. 7.33±9.17, p = 0.042), PRF1 (21.67±26.34 vs. 10.67±11.65, p = 0.039), and CD70 (1.45±1.63 vs. 0.67±0.28, p = 0.011). A positive correlation was observed between transcript levels of CD40LG and ITGAL (r = 0.477, p = 0.004) as well as between CD40LG and PRF1 (r = 0.557, p = 0.001). Transcript levels of KIR2DL4 were higher than controls' but it did not reach statistical significance (1.36±3.52 vs. 0.22±0.79, p = 0.560). A tight relationship with global DNA hypomethylation as well as with the expression of most of the DNA methylation-related genes was observed, especially for ITGAL, PRF1, and CD40LG. CONCLUSIONS: ITGAL, PRF1, and CD70 are overexpressed in SLE CD4(+) T cells. The tight association of CD40LG with ITGAL and PRF1 leads us to infer that it probably contributes to the pathogenesis of the disease. The apparent simultaneous regulation between their expression and the global DNA hypomethylation as well as with the transcription of many DNA methylation-related enzymes, reinforces the idea that epigenetic mechanisms are responsible for the deregulation of ITGAL, PRF1, and CD40LG.
Subject(s)
DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA-Binding Proteins/metabolism , Endodeoxyribonucleases/metabolism , Epigenesis, Genetic , Gene Expression , Lupus Erythematosus, Systemic/genetics , Adult , Aged , CD11a Antigen/genetics , CD11a Antigen/metabolism , CD27 Ligand/genetics , CD27 Ligand/metabolism , CD4-Positive T-Lymphocytes/metabolism , CD40 Ligand/genetics , CD40 Ligand/metabolism , Case-Control Studies , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methylation , DNA-Binding Proteins/genetics , Endodeoxyribonucleases/genetics , Female , Humans , Lupus Erythematosus, Systemic/enzymology , Lupus Erythematosus, Systemic/metabolism , Male , Middle Aged , Perforin , Pore Forming Cytotoxic Proteins/genetics , Pore Forming Cytotoxic Proteins/metabolism , Receptors, KIR2DL4/genetics , Receptors, KIR2DL4/metabolism , Statistics, Nonparametric , Young AdultABSTRACT
OBJECTIVES: Xenotropic murine leukemia virus-related virus (XMRV)-specific proviral DNA has been recently detected in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Since chronic fatigue is commonly reported in patients with systemic lupus erythematosus (SLE) we aimed at testing the presence of this virus in these patients. METHODS: Ninety-five SLE patients, 45 of whom had a Fatigue Severity Scale score higher than 3, were included. Molecular analyses were performed by PCR from DNA obtained from the whole blood of both SLE patients and 50 healthy controls. RESULTS: None of the 145 samples analyzed yielded the specific XMRV PCR product. CONCLUSIONS: We conclude that XMRV is not detected in blood neither from SLE patients nor from healthy controls. It leads to infer that other environmental and biological triggers (different from XMRV) may account for the increased levels of fatigue over the course of SLE.
