Ganjalikhani-Hakemi Mazdak, Yazdani Reza, Sherkat Roya, Homayouni Vida, Masjedi Mohsen, Hosseini Mohsen
Cellular and Molecular Immunology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran.
Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Res Med Sci. 2014 Mar;19(Suppl 1):S30-5.
Common variable immunodeficiency (CVID) is characterized by a deficiency in the immune system with a heterogeneous collection of disorders resulting in antibody deficiency and recurrent infections. T helper 17 (Th17) cells promote B-cell survival and synergize with the B-cell activating factor to induce their differentiation into the plasma cells. A sub-population of innate lymphoid cells (ILCs) also produces interleukin 17 (IL-17). This study aimed to measure the Th17 specific genes and ILCs counts in the CVID patients in comparison with control subjects.
Total messenger ribonucleic acid (mRNA) was extracted from the whole blood samples of 10 CVID patients and 10 healthy individuals. IL-17, retinoic acid receptor-related orphan receptor C2 (RORC2), IL-23R, and IL-9 gene expression were measured using the quantitative reverse transcriptase-polymerase chain reaction. Count of lineage negative/CD127(+)/CD90(+) ILCs in the blood samples was performed by the flow cytometry method.
The transcript levels of IL-17 and RORC2 in CVID patients was strongly lower than control subjects (P = 0.049 and P = 0.046, respectively), but slight reduction in the IL-23R expression (P = 0.252) have seen in the CVID patients. Accordingly, the number of ILCs decreased significantly (P = 0.04). Interestingly, IL-9 mRNA level was more significantly in the CVID patients (P = 0.001).
The results presented in this study show that the Th17 cell specific genes expression (as the determiner Th17 cells) and ILCs (another lymphoid source of IL-17) are decreased in patients with CVID and this could be an explanation for the defect of their humoral immune response. In addition, elevation of the IL-9 gene expression may shed a new light into the way toward the understanding of the mechanism of autoimmunity in the CVID patients.
普通可变免疫缺陷（CVID）的特征是免疫系统缺陷，伴有多种导致抗体缺陷和反复感染的疾病。辅助性T细胞17（Th17）细胞促进B细胞存活，并与B细胞活化因子协同作用，诱导其分化为浆细胞。一部分天然淋巴细胞（ILC）也产生白细胞介素17（IL-17）。本研究旨在测量CVID患者与对照受试者中Th17特异性基因和ILC计数。
从10例CVID患者和10名健康个体的全血样本中提取总信使核糖核酸（mRNA）。使用定量逆转录聚合酶链反应测量IL-17、视黄酸受体相关孤儿受体C2（RORC2）、IL-23R和IL-9基因表达。通过流式细胞术方法对血样中的谱系阴性/CD127（+）/CD90（+）ILC进行计数。
CVID患者中IL-17和RORC2的转录水平明显低于对照受试者（分别为P = 0.049和P = 0.046），但在CVID患者中观察到IL-23R表达略有降低（P = 0.252）。相应地，ILC数量显著减少（P = 0.04）。有趣的是，CVID患者中IL-9 mRNA水平更高（P = 0.001）。
本研究结果表明，CVID患者中Th17细胞特异性基因表达（作为Th17细胞的决定因素）和ILC（IL-17的另一种淋巴细胞来源）减少，这可能是其体液免疫反应缺陷的一个解释。此外，IL-9基因表达的升高可能为理解CVID患者自身免疫机制的方向提供新的线索。
