MicroRNA Expressions in PMBCs, CD4+, and CD8+ T-Cells from Patients Suffering from Autoimmune Addison's Disease

Abstract

Autoimmune Addison's disease (AD) is a rare but potentially life threatening disease. The exact etiology of the immune response to the adrenal gland is still unknown. MicroRNAs (miRNAs) critically control gene-expression and play an important role in regulating the immune response. The aim of this study was to determine key immunoregulatory miRNAs influencing autoimmune adrenal insufficiency. For this purpose selected miRNAs were amplified by a semiquantitative SYBR Green PCR from blood mononuclear cells and after purification from CD4+ and CD 8+ cells of 6 patients with autoimmune adrenal insufficiency and 10 healthy controls. In CD4+ T-cells miRNA 181a*_1 (18.02 in AD vs. 11.99 in CG, p=0.0047) is significantly increased whereas miRNA 200a_1 (12.48 in AD vs. 19.40 in CG, p=0.0003) and miRNA 200a_2* (8.59 in AD vs. 17.94 in CG, p=0.0160) are significantly decreased. miRNA 200a_1 (12.37 in AD group vs. 18.12 in control group, p=0.001) and miRNA 200a_2* (10.72 in AD group vs. 17.84 in control group, p=0.022) are also significantly decreased in CD8+ T-cells. This study could show for the first time a significant change of three defined miRNAs in PBMCs, CD4+, and CD8+ T-cells of autoimmune AD patients in vivo. These data may help to better understand the cause of the autoimmune processes leading to autoimmune AD. They extend our very limited knowledge concerning miRNAs in autoimmune Addison's disease.

HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity

“…PGA is characterized by the coexistence of at least 2 autoimmune endocrine disorders, that is, type 1 diabetes (T1D) or autoimmune thyroid disease (AITD) with Addison's disease [4,5]. Significantly impaired microRNA expressions in PBMCs, CD4 + , and CD8 + T-cells were noted in patients with Addison's disease [6]. With 10 % of all autoimmune patients affected, AITD, either Graves' disease (GD) or Hashimoto's thyroiditis (HT), are the most common autoimmune disorders, followed by T1D with a significantly lower prevalence of 0.7 % [7].…”

Overexpression of miR-7977 in CD4+ T cells is associated with multiplex autoimmunity in patients with Addison’s disease

“…These include miR-146a, miR-155, and miR-375 deregulated in T1D and AITD, as well as miR-22 and miR-451, upregulated in HT and GD (20,21,44). Furthermore, miR-200a_1 and miR-200a_2* were down-regulated in CD4+ and CD8+ cells in AD and both AITD forms (19,27). Some deregulated miRNA are shared by organ-specific and systemic autoimmune conditions, such as miR-21, miR-146a and miR-155 in T1D, SLE, and rheumatoid arthritis (14).…”

“…Until now, only a few selected miRNAs were investigated in AD. A semi-quantitative analysis in six affected individuals revealed increased expression of miRNA 181a*_1 in CD4+ T cells and downregulated expression of miRNA 200a_1 and 200a_2* in CD4+ and CD8+ cells compared to healthy controls (27). A better understanding of the role of miRNAs in autoimmunity might indicate plausible therapeutic targets for future interventions aimed at modulating the disturbed function of the immune system (14,23).…”

The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

“…During the past two decades, 2588 mature Mirs have been described in humans. The roles of Mirs have been described in several diseases, including cancers, [21–23] coronary diseases, [24,25] autoimmune diseases, [26–28] and viral infections [29,30]. Although several studies have emerged describing Mir dysregulation in CF (reviewed in [31]), Mir involvement in CF needs further investigation and elucidation.…”