ABSTRACT

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease with a heterogeneous genetic background. Lipopolysaccharide-responsive beige-like anchor (LRBA), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have important regulatory roles in the immune responses. Here, we have investigated the expression of LRBA and CTLA-4 proteins in CVID patients with at least one presentation of early-onset occurrence, autoimmunity, or enteropathy. In this study, 20 newly diagnosed CVID patients without infection only phenotype, and ten healthy individuals were enrolled. The expressions of LRBA and CTLA-4 proteins were assessed by western blotting and flow cytometry, respectively. The patients were divided into two groups of autoimmunity-positive (11 cases) and autoimmunity-negative (9 patients). LRBA and CTLA-4 expressions were significantly lower in autoimmune-positive patients than in healthy individuals (P = .03 and P = .03, respectively). Autoimmune-negative patients had lower expression of LRBA and CTLA-4 than the control group, although it was not significant. There was a positive correlation between the expressions of LRBA and CTLA-4 in both groups of patients (P < .05). Furthermore, the highest frequency of LRBA (85.7%) and CTLA-4 (71.4%) defects was detected in those with concomitant presence of autoimmunity, enteropathy, and early-onset occurrence. Concurrent presence of autoimmunity, enteropathy, and early-onset occurrence in CVID patients could be indicative of a lack of expression in LRBA and CTLA-4 proteins. This could be helpful in early diagnosis and initiation of appropriate treatment in these patients prior to genetic confirmation.

摘要

常见变异型免疫缺陷（CVID）是一种具有异质遗传背景的原发性免疫缺陷疾病。脂多糖反应性米色样锚 (LRBA) 以及细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 在免疫反应中具有重要的调节作用。在这里，我们研究了 CVID 患者中 LRBA 和 CTLA-4 蛋白的表达，这些患者至少有一种早发性、自身免疫性或肠病的表现。在这项研究中，20 名新诊断的无感染表型的 CVID 患者和 10 名健康个体被纳入研究。分别通过蛋白质印迹和流式细胞术评估LRBA和CTLA-4蛋白的表达。将患者分为自身免疫阳性（11例）和自身免疫阴性（9例）两组。P = .03 和P = .03，分别）。自身免疫阴性患者的 LRBA 和 CTLA-4 表达低于对照组，但不显着。两组患者LRBA与CTLA-4表达均呈正相关（P <.05）。此外，LRBA (85.7%) 和 CTLA-4 (71.4%) 缺陷的最高频率在同时存在自身免疫、肠病和早发性发生的患者中检测到。CVID 患者同时存在自身免疫、肠病和早发性可能表明 LRBA 和 CTLA-4 蛋白缺乏表达。这可能有助于在基因确认之前对这些患者进行早期诊断和开始适当的治疗。