Expression signature of microRNA-181-a reveals its crucial role in the pathogenesis of paediatric systemic lupus erythematosus.

OBJECTIVES

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by self-reactive antibodies due to failure of selection in both B and T lymphocytes leading to immune intolerance accompanied by increased rate of apoptosis and deficiency in the clearance of the apoptotic cells. Micro RNAs regulate posttranscriptional gene expression and have been recently identified to regulate cellular differentiation, establishing immunological tolerance and are involved in the pathogenesis of several diseases. miR-181-a, expressed in haematopoietic cell lineage, has shown to be an important modulator of B and T cell differentiation, maturation and function. This study aims to identify the expression signature of miR-181-a in the peripheral blood of paediatric SLE and its regulatory effect on the consequent expression of its target gene PCAF.

METHODS

Twenty SLE paediatrics patients, 9 healthy controls and 4 FMF patients were enrolled in this study. The relative expression of miR-181-a, miR-223, PCAF and Hdm2 were performed using quantitative real time PCR.

RESULTS

For the first time we show that miR-181-a was significantly downregulated in SLE pediatrics as compared to healthy controls. Furthermore, miR-181-a showed significant difference in its expression among groups with different SLEDAI scores. This special signature of miR-181-a expression is unique to SLE as compared to FMF samples which showed a parallel expression to healthy controls. PCAF was upregulated in SLE patients compared to healthy controls, which has an impact on the ubiquitination of Hdm2 and hence releases p53 leading to the induction of apoptosis.

CONCLUSIONS

miR-181-a plays an important role in SLE pathogenesis.