Primary antibody deficiencies (PAD) represent a heterogeneous group of disorders, with common variable immunodeficiency being the most common with clinical significance. The main phenotypic defect resides in the inability of B cells to produce antibodies, and the cornerstone of therapy is immunoglobulin replacement treatment in order to fight infections. However, the management of the other inflammatory manifestations is inadequate, reinforcing the hypothesis that a complex genetic background affecting additional cell populations, such as polymorphonuclear cells (PMN) and monocytes, influences the expression of the clinical phenotype of the disease. In this study, we investigated by flow cytometry in different conditions (resting state, and after isolation and incubation, with and without stimuli) the expression pattern of several markers on PMN and monocytes, indicative of their maturation, capacity for chemotaxis, adhesion, opsonization, migration, and phagocytosis in 25 PAD patients, 12 healthy blood donors, and 4 septic patients. In this context, we also analyzed patients before and after the initiation of replacement treatment, as well as an untreated patient in different clinical conditions. Interestingly, we observed that PAD patients exhibit a chronic activation status of the innate immunity compartment, along with several differences in the expression of activation, maturation, and adhesion markers, with respect to different clinical conditions. Moreover, immunoglobulin replacement treatment had a favorable effect on PMN, as it was expressed by a more mature and less activated phenotype on basal state cells, and an enhanced activation capacity after LPS exposure. Thus, we conclude that PAD patients display a persistent innate immune cell activation, which is probably associated with the chronic inflammatory stress, usually observed in these disorders.

中文翻译：

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原发性抗体缺乏症患者先天免疫的持续激活

初级抗体缺陷 (PAD) 代表一组异质性疾病，常见的可变免疫缺陷是最常见的具有临床意义的疾病。主要的表型缺陷在于 B 细胞不能产生抗体，治疗的基石是免疫球蛋白替代治疗以对抗感染。然而，其他炎症表现的管理不充分，强化了影响额外细胞群（如多形核细胞 (PMN) 和单核细胞）的复杂遗传背景影响疾病临床表型表达的假设。在这项研究中，我们通过流式细胞术在不同条件下（静息状态，以及分离和孵育后，有和没有刺激）几种标志物在 PMN 和单核细胞上的表达模式，表明它们在 25 名 PAD 患者、12 名健康献血者和 4 名败血症患者中的成熟、趋化能力、粘附、调理、迁移和吞噬作用。在这种情况下，我们还分析了替代治疗开始前后的患者，以及不同临床条件下未经治疗的患者。有趣的是，我们观察到 PAD 患者表现出先天免疫区室的慢性激活状态，以及激活、成熟和粘附标志物表达的一些差异，与不同的临床条件有关。此外，免疫球蛋白替代治疗对 PMN 有良好的影响，因为它在基础状态细胞上表现出更成熟和更少活化的表型，以及在 LPS 暴露后增强的活化能力。因此，我们得出结论，PAD 患者表现出持续的先天免疫细胞激活，这可能与慢性炎症应激有关，通常在这些疾病中观察到。