Key result
In 13 SLE subjects and 8 healthy controls, SLE T cells demonstrated A to I hypo-editing followed by up-regulation of PDE8A1 transcripts compared to normal T cells.
Case-Control (n=21)
Altered ADAR-mediated RNA editing of PDE8A1 transcripts in T cells may contribute to the immunopathogenesis of systemic lupus erythematosus.
PDE8A1 hypo-editing may contribute to SLE T-cell dysfunction; hypothesis-generating and leaves open causal or therapeutic roles.
The aetiopathogenesis of the abnormal immune response in systemic lupus erythematosus (SLE) remains incompletely understood. We and other investigators demonstrated altered expression of adenosine deaminase that act on RNA (ADAR) genes in SLE patients. Based on this information, we hypothesize that the altered expression and function of ADAR enzymes is a mechanism for the immunopathogenesis of SLE. ADARs edit gene transcripts through site-specific conversion of adenosine to inosine by hydrolytic deamination at C6 of the adenosine. Thirteen SLE subjects and eight healthy controls were studied. We assessed the role of ADAR enzymes in editing of PDE8A1 gene transcripts of normal and SLE T cells. These studies demonstrated the occurrence of ADAR-catalysed altered and site-selective editing profile of specific sites in the PDE8A1 gene transcripts of normal and SLE T cells. Two hot spots for A to I editing were observed in the PDE8A1 transcripts of normal and SLE T cells. A fundamental finding of this study is A to I hypo-editing followed by up-regulation of PDE8A1 transcripts in SLE T cells. These results are confirmed by analysing PDE8A1 transcripts of normal T cells activated with type I interferon-alpha. It is proposed that, the altered expression of ADAR enzymes tilt the balance of editing machinery and alter editing in SLE transcriptome. Such altered editing may contribute to the modulation of gene regulation and ultimately, immune functions in SLE and play an important role in the initiation and propagation of SLE pathogenesis.
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Orlowski et al. (2008) conducted a case-control in Systemic lupus erythematosus (n=21). Systemic lupus erythematosus vs. Healthy controls was evaluated on A to I editing of PDE8A1 gene transcripts. In 13 SLE subjects and 8 healthy controls, SLE T cells demonstrated A to I hypo-editing followed by up-regulation of PDE8A1 transcripts compared to normal T cells.
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