P089 Suppression of a HLA-B encoded microrna upregulates the expression of heavy chain IGA (IGHA1) transcript in human primary B-cells

Abstract

Aim Our previous work has shown that the HLA-B encoded miR-6891-5p influences the expression of about 200 transcripts, including the transcript encoding for the heavy chain of IgA, in a B cell line. We showed that the expression of heavy chain of IgA was up-regulated when miR-6891-5p activity was suppressed (doi: 10.3389/fimmu.2017.00583). In this work we aimed to determine whether increased expression of heavy chain of IgA transcript is also possible by suppressing miR-6891-5p activity in human primary B-cells. Methods Human primary B-cells from a total of 12 human volunteers were analyzed. One of the samples was from an IgA deficient patient ( IGHA1 expression. The results are shown in fold increase of the antisense vs the scrambled mi-RNA-5p construct. We assessed whether suppression of miR-6891-5p activity can increase expression of heavy chain of IgA in human primary B-cells. Results Suppression of miR-6891-5p activity in human primary B-cells led to IGHA1 up-regulation in 11 antisense miR-6891-5p transduced samples. The average upregulation of the 11 samples was 2.48-fold. (range of increase 1.04–7.88X). The B cells of the IgA deficient sample upon transduction with antisense miR-6891-5p showed a 6.75-fold upregulation relative to scrambled control. We are in the process of evaluating more IgA deficient subjects. Conclusions We show that the suppression of miR-6891-5p activity can upregulate IGHA1 expression in primary human B-cells. This upregulation was higher in the IgA deficient sample compared to average of the 11 non-IgA deficient samples. MicroRNAs are known for fine-tuning gene expression. Modifying the activity of the miR-6891-5p, a HLA-B intronic sequence, in an IgA deficient subject restores the expression levels of IGHA1 transcript in primary B cells.