Department of Clinical Immunology and Transfusion Medicine, and Department of Biomedical and Clinical Sciences, Linköping University, S-58185, Linköping, Sweden.
Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
J Clin Immunol. 2023 Dec 22;44(1):21. doi: 10.1007/s10875-023-01618-0.
Common variable immunodeficiency (CVID) is a primary antibody deficiency that commonly manifests as recurrent infections. Many CVID patients also suffer from immune dysregulation, an inflammatory condition characterized by polyclonal lymphocytic tissue infiltration and associated with increased morbidity and mortality. The genetic cause is unknown in most CVID patients and epigenetic alterations may contribute to the broad range of clinical manifestations. MicroRNAs are small non-coding RNAs that are involved in epigenetic modulation and may contribute to the clinical phenotype in CVID.
Here, we determined the circulating microRNAome and plasma inflammatory proteins of a cohort of CVID patients with various levels of immune dysregulation and compared them to healthy controls. A set of deregulated microRNAs was validated by qPCR and correlated to inflammatory proteins and clinical findings.
Levels of microRNA-34a correlated with 11 proteins such as CXCL9, TNF, and IL10, which were predicted to be biologically connected. Moreover, there was a negative correlation between mir-34 levels and the number of naïve CD4 T cells in CVID.
Collectively, our data show that microRNAs correlate with the inflammatory response in CVID. Further investigations are needed to elucidate the role of miRNAs in the development of CVID-related immune dysregulation.
普通变异型免疫缺陷病（CVID）是一种常见的抗体缺陷病，常表现为反复感染。许多 CVID 患者还患有免疫失调，这是一种以多克隆淋巴细胞组织浸润为特征的炎症性疾病，与发病率和死亡率增加有关。大多数 CVID 患者的遗传原因尚不清楚，表观遗传改变可能导致广泛的临床表现。microRNA 是参与表观遗传调节的小非编码 RNA，可能导致 CVID 的临床表型。
在这里，我们确定了一组具有不同程度免疫失调的 CVID 患者的循环 microRNA 组和血浆炎症蛋白，并将其与健康对照组进行比较。一组失调的 microRNA 通过 qPCR 进行验证，并与炎症蛋白和临床发现相关联。
microRNA-34a 的水平与 CXCL9、TNF 和 IL10 等 11 种蛋白质相关，这些蛋白质被预测具有生物学相关性。此外，CVID 中 mir-34 水平与幼稚 CD4 T 细胞数量呈负相关。
总的来说，我们的数据表明 microRNA 与 CVID 中的炎症反应相关。需要进一步的研究来阐明 microRNA 在 CVID 相关免疫失调发展中的作用。
