Hawari Iman, Ericsson Johan, Kabeer Basirudeen Syed Ahamed, Chaussabel Damien, Alsulaiti Asma, Sharari Sanaa A, Maccalli Cristina, Khan Faiyaz Ahmad, Hussain Khalid
College of Health & Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha P.O. Box 34110, Qatar.
Research Branch, Sidra Medicine, Doha P.O. Box 26999, Qatar.
Biology (Basel). 2022 Apr 18;11(4):612. doi: 10.3390/biology11040612.
The scope of this study is to show that DM in a LRBA-deficient patient with a stop codon mutation (c.3999 G > A) was not mediated through autoimmunity. We have evaluated the ability of the proband’s T cells to be activated by assessing their CTLA-4 expression. A nonsignificant difference was seen in the CTLA-4 expression on CD3+ T cells compared to the healthy control at basal level and after stimulation with PMA/ionomycin. Blood transcriptomic analysis have shown a remarkable increase in abundance of transcripts related to CD71+ erythroid cells. There were no differences in the expression of modules related to autoimmunity diseases between the proband and pooled healthy controls. In addition, our novel findings show that siRNA knockdown of LRBA in mouse pancreatic β-cells leads reduced cellular proinsulin, insulin and consequently insulin secretion, without change in cell viability in cultured MIN6 cells.
本研究的范围是表明，在一名携带终止密码子突变（c.3999 G > A）的LRBA缺陷患者中，糖尿病并非通过自身免疫介导。我们通过评估先证者T细胞的CTLA-4表达来评估其被激活的能力。与健康对照相比，在基础水平以及用佛波酯/离子霉素刺激后，CD3+ T细胞上的CTLA-4表达无显著差异。血液转录组分析显示，与CD71+红系细胞相关的转录本丰度显著增加。先证者与汇总的健康对照之间，与自身免疫性疾病相关模块的表达没有差异。此外，我们的新发现表明，在小鼠胰腺β细胞中敲低LRBA的siRNA会导致细胞内胰岛素原、胰岛素减少，从而导致胰岛素分泌减少，而在培养的MIN6细胞中细胞活力没有变化。
