Myeloid Cell Laboratory, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040, Madrid, Spain.
Hospital Universitario Clínico San Carlos, IML and IdSSC, Madrid, Spain.
J Clin Immunol. 2022 Jul;42(5):1093-1105. doi: 10.1007/s10875-022-01277-7. Epub 2022 Apr 29.
Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14 cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.
常见变异性免疫缺陷病（CVID）是最常见的原发性免疫缺陷病，包括以低丙种球蛋白血症和抗体反应受损为特征的异质性综合征。CVID 患者经常遭受反复感染和炎症。目前，免疫球蛋白替代疗法（IgRT）是预防 CVID 患者感染和改善免疫改变的一线治疗方法。静脉注射免疫球蛋白（IVIg）是一种高度纯化的多特异性 IgG 制剂，用于治疗免疫缺陷以及自身免疫和炎症性疾病，因为 IVIg 对先天和适应性免疫细胞具有免疫调节和抗炎作用。为了确定 IVIg 在体内治疗 CVID 的作用机制，我们确定了 IVIg 输注对 CVID 患者外周血单个核细胞转录组的影响，发现外周血单核细胞是 IVIg 在体内的主要靶标，并且 IVIg 触发了人类单核细胞获得抗炎基因谱。此外，IVIg 改变了外周血单核细胞亚群的相对比例，并增强了具有类似于单核细胞髓系来源抑制细胞（MDSC）的转录、表型和功能特征的 CD14 细胞的比例。因此，我们的结果表明，CD14+MDSC 样细胞可能有助于 IVIg 在 CVID 和其他炎症性疾病中的免疫调节作用。
