Division of Molecular Virology, Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusions Medicine, and Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden.
Department of Clinical Immunology and Transfusions Medicine, and Department of Biomedicine and Clinical Sciences, Linköping University, Linköping, Sweden.
J Allergy Clin Immunol. 2020 Aug;146(2):417-428. doi: 10.1016/j.jaci.2020.01.046. Epub 2020 Feb 11.
Common variable immunodeficiency (CVID) is a disorder characterized by antibody deficiency. A significant fraction of the patients suffer from immune dysregulation, which leads to increased morbidity and mortality. The pathogenesis of this condition is poorly understood.
Our aim was to find out whether the plasma protein signature in CVID is associated with clinical characteristics and lymphocyte aberrations.
A highly sensitive proximity extension assay was used for targeted profiling of 145 plasma proteins in 29 patients with CVID. Phenotyping of peripheral lymphocytes was done by flow cytometry. The findings were correlated with the burden of immune dysregulation.
Unsupervised clustering of plasma protein profiles identified 2 distinct groups of patients with CVID that differed significantly in terms of the degree of complications due to immune dysregulation and in terms of the frequency of activated B- and T-cell subpopulations. Pathway analysis identified IFN-γ and IL-1β as the top enriched upstream regulators associated with higher grade of immune dysregulation. In addition, CVID was found to be associated with increased plasma levels of the B-cell-attracting chemokine CXCL13.
Clustering based on plasma protein profiles delineated a subgroup of patients with CVID with activated T cells and clinical complications due to immune dysregulation. Thus, data indicate that CVID-associated immune dysregulation is a T1-mediated inflammatory process driven by the IFN-γ pathway.
普通变异型免疫缺陷病（CVID）是一种以抗体缺陷为特征的疾病。相当一部分患者存在免疫失调，导致发病率和死亡率增加。这种疾病的发病机制尚未完全了解。
我们旨在了解 CVID 患者的血浆蛋白特征是否与临床特征和淋巴细胞异常有关。
采用高灵敏度的邻近延伸分析技术对 29 例 CVID 患者的 145 种血浆蛋白进行靶向分析。通过流式细胞术对外周淋巴细胞进行表型分析。将结果与免疫失调的负担相关联。
对血浆蛋白谱进行无监督聚类，可将 CVID 患者分为 2 个不同的组，这两组在免疫失调相关并发症的严重程度以及激活的 B 细胞和 T 细胞亚群的频率方面存在显著差异。通路分析确定 IFN-γ 和 IL-1β 是与较高免疫失调程度相关的最富集的上游调节剂。此外，还发现 CVID 与 B 细胞趋化因子 CXCL13 的血浆水平升高有关。
基于血浆蛋白谱的聚类可将 CVID 患者分为亚组，这些患者存在 T 细胞激活和免疫失调引起的临床并发症。因此，数据表明 CVID 相关的免疫失调是由 IFN-γ 通路驱动的 T1 介导的炎症过程。
