Institute of Liver Studies, King's College Hospital, London, UK.
Curr Opin Rheumatol. 2011 Jan;23(1):114-8. doi: 10.1097/BOR.0b013e3283412f4a.
To review studies that have examined underlying genetic and immunological aspects of IgG4-related disease.
Genetic studies have suggested that several human leukocyte antigen (HLA) and non-HLA haplotypes/genotypes are associated with susceptibility to IgG4-related disease or to disease relapse after steroid therapy. Among several autoantibodies identified so far, autoantibodies against lactoferrin and carbonic anhydrase II are most frequently detected in serum of IgG4-disease patients. However, it has not been well clarified whether or not those autoantibodies belong to an IgG4 subclass. Studies that have demonstrated molecular mimicry between Helicobacter pylori and constituents of pancreatic epithelial cells suggest that gastric H. pylori infection triggers autoimmune pancreatitis in genetically predisposed individuals through antibody cross-reactivity. Recently, T-helper 2 immune reaction has been suggested to be predominant in IgG4-related disease. Interestingly, regulatory immune reactions are activated in IgG4-related disease, and regulatory cytokines interleukin-10 and transforming growth factor-b have been suggested, respectively, to play important roles in IgG4 class switch and fibroplasia.
Autoimmunity has been considered the most probable pathogenesis of IgG4-related disease, but has not been completely proved so far. A breakthrough study to detect a specific autoantigen, autoantibody, or pathogen is necessary.
综述 IgG4 相关疾病潜在遗传和免疫方面的研究。
遗传研究表明，几种人类白细胞抗原（HLA）和非 HLA 单倍型/基因型与 IgG4 相关疾病易感性或类固醇治疗后疾病复发有关。在迄今为止鉴定的几种自身抗体中，针对乳铁蛋白和碳酸酐酶 II 的自身抗体最常存在于 IgG4 疾病患者的血清中。然而，这些自身抗体是否属于 IgG4 亚类尚未得到很好的阐明。已经证明幽门螺杆菌和胰腺上皮细胞成分之间存在分子模拟的研究表明，通过抗体交叉反应，胃幽门螺杆菌感染在遗传易感个体中引发自身免疫性胰腺炎。最近，辅助性 T 细胞 2 免疫反应被认为在 IgG4 相关疾病中占主导地位。有趣的是，在 IgG4 相关疾病中激活了调节性免疫反应，分别有研究提出白细胞介素-10 和转化生长因子-β在 IgG4 类别转换和纤维化中发挥重要作用。
自身免疫被认为是 IgG4 相关疾病最可能的发病机制，但迄今尚未得到完全证实。有必要进行一项检测特定自身抗原、自身抗体或病原体的突破性研究。
