ABSTRACT

The loss of tolerance to self-antigens is the unequivocal “red line” of autoimmunity: both development of autoreactive T and B cells and production of polyclonal autoantibodies represent seminal keys to the pathogenesis of protean autoimmune diseases. Most of these autoantibodies are immunoglobulins G (IgG), functionally distinguished in four subclasses named IgG1, IgG2, IgG3, and IgG4, due to structural differences in the hinge and heavy chain constant regions. Different studies analyzed serum levels of IgG subclasses in the course of different disorders, showing that they might have a pathogenic role by regulating interactions among immunoglobulins, Fc-gamma receptors, and complement. To date, the mechanisms promoting different IgG subclasses distribution during the natural history of most autoimmune diseases remain somewhat unclear. Evidence from the medical literature shows that the serum IgG profile is peculiar for many autoimmune diseases, suggesting that different subclasses could be specific for the underlying driving autoantigens. A better knowledge of IgG subsets may probably help to elucidate their pathological task, but also to define their relevance for diagnostic purposes, patients’ personalized management, and prognosis assessment.

摘要

对自身抗原的耐受性丧失是自身免疫的明确“红线”：自身反应性 T 细胞和 B 细胞的发展以及多克隆自身抗体的产生都是多变的自身免疫疾病发病机制的关键。大多数这些自身抗体是免疫球蛋白 G (IgG)，由于铰链和重链恒定区的结构差异，在功能上分为四个亚类，分别称为 IgG1、IgG2、IgG3 和 IgG4。不同的研究分析了不同疾病过程中 IgG 亚类的血清水平，表明它们可能通过调节免疫球蛋白、Fc-γ 受体和补体之间的相互作用而具有致病作用。迄今为止，在大多数自身免疫性疾病的自然病程中促进不同 IgG 亚类分布的机制仍不清楚。来自医学文献的证据表明，血清 IgG 谱对于许多自身免疫疾病来说是独特的，这表明不同的亚类可能对潜在的驱动自身抗原具有特异性。更好地了解 IgG 亚群可能有助于阐明其病理任务，但也有助于确定其与诊断目的、患者个性化管理和预后评估的相关性。