Motta Rodrigo V, Culver Emma L
Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Front Immunol. 2024 Feb 16;15:1272084. doi: 10.3389/fimmu.2024.1272084. eCollection 2024.
Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.
免疫球蛋白是体液免疫反应的重要组成部分。IgG4抗体是最不常见的亚类，具有独特的结构和功能特性。在本综述中，我们讨论了IgG4类别转换和B细胞产生。我们综述了IgG4抗体在过敏反应、蠕虫感染和恶性肿瘤中的重要性。我们讨论了它们在变应原特异性免疫治疗中的抗炎和致耐受性作用，以及在寄生虫感染和肿瘤细胞中逃避免疫系统的能力。然后，我们重点关注IgG4自身抗体和自身抗原在IgG4自身免疫性疾病和IgG4相关疾病中的作用，强调它们之间重要的相似点和不同点。在IgG4自身免疫性疾病中，发病机制基于IgG4抗体与自身抗原结合并破坏内环境稳态的直接作用。在IgG4相关疾病中，受累器官被表达IgG4的浆细胞浸润，IgG4抗体也可能直接靶向多种自身抗原或作为疾病的一种附带现象而过度表达。这些抗原驱动的过程需要关键的T细胞和B细胞相互作用。最后，我们探讨了目前我们知识上的空白以及如何填补这些空白。
