Immunoglobulin G4-related disease (IgG4-RD) is the name applied to a corticosteroid and/or B-cell depletion responsive illness, in which patients present with the consequences of usually multiorgan, relapsing and remitting, fibroinflammation.1 The disease is histologically characterised by obliterative phlebitis, storiform fibrosis and a dense lymphoplasmacytic infiltrate.2 IgG4-RD is not a new disease, but is benefiting from the application of new technologies in the pursuit of better biological understanding. The histologic enrichment of IgG4-expressing plasma cells is a diagnostic hallmark of disease that additionally serves as a biological phenomenon driving scientific evaluation.3 Key disease themes have evolved to include a large clonal expansion of activated plasmablasts and CD4+ cytotoxic, inflammatory and profibrotic lymphocytes. Therapeutically, a reduced frequency of CD4+ cytotoxic lymphocytes are seen after B-cell depletion; such therapy may consequently impact on antigen presentation.4–6 To date, the activity of IgG4-RD is not readily tracked by disease biomarkers with even serum IgG4 concentration remaining an imperfect diagnostic and prognostic tool for many patients.7 IgG4 molecules have structural and functional characteristics suggesting anti-inflammatory and tolerance-inducing effects,8 9 and in IgG4-RD a reported oligoclonal reactivity to multiple antigens.4 10 In Gut , Hubers et al describe a body of work that identifies the first IgG4 autoantibody against an antigen which appears to be specific to IgG4-RD (IgG4-associated cholangitis (IAC) and autoimmune pancreatitis (AIP)), at the exclusion of its major differential diagnoses: primary sclerosing cholangitis and cholangiocarcinoma.11 The authors demonstrate that patients with IgG4-RD raise IgG1 and IgG4 in their sera that recognise a 56 kDa cytosolic protein in an immortalised cell line lysate (H69 cholangiocytes) and in human liver lysate. Both IgG1 and IgG4 antibodies recognise the same 56 kDa protein, and subsequent label-free quantitative liquid chromatography-tandem mass spectrometry analysis and immunoprecipitation identifies the cytosolic protein, Annexin A11, as the target. Annexin A11 IgG4 …

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解读 IgG4 相关疾病的生物学：特异性抗原和疾病？

免疫球蛋白 G4 相关疾病 (IgG4-RD) 是适用于皮质类固醇和/或 B 细胞耗竭反应性疾病的名称，在这种疾病中，患者通常会出现多器官、复发和缓解的纤维炎症的后果。1 该疾病在组织学上具有特征闭塞性静脉炎、席纹状纤维化和致密的淋巴浆细胞浸润。2 IgG4-RD 不是一种新疾病，而是受益于新技术的应用，以寻求更好的生物学理解。表达 IgG4 的浆细胞的组织学富集是疾病的诊断标志，也是推动科学评估的生物学现象。 3 关键疾病主题已演变为包括活化浆母细胞和 CD4+ 细胞毒性、炎症和促纤维化淋巴细胞的大量克隆扩增。在治疗上，在 B 细胞耗竭后，CD4+ 细胞毒性淋巴细胞的频率降低；因此，这种治疗可能会影响抗原呈递。 4-6 迄今为止，疾病生物标志物不容易追踪 IgG4-RD 的活性，即使是血清 IgG4 浓度，对于许多患者来说仍然是一种不完善的诊断和预后工具。 7 IgG4 分子具有结构和功能特征表明抗炎和耐受诱导作用，8 9 并且在 IgG4-RD 中报道了对多种抗原的寡克隆反应性 4 10。似乎对 IgG4-RD（IgG4 相关胆管炎 (IAC) 和自身免疫性胰腺炎 (AIP)）具有特异性，但排除了其主要鉴别诊断：原发性硬化性胆管炎和胆管癌。11 作者证明，IgG4-RD 患者的血清中 IgG1 和 IgG4 可识别永生化细胞系裂解物（H69 胆管细胞）和人类肝脏裂解物中的 56 kDa 胞质蛋白。IgG1 和 IgG4 抗体均识别相同的 56 kDa 蛋白，随后的无标记定量液相色谱-串联质谱分析和免疫沉淀将胞质蛋白膜联蛋白 A11 确定为靶标。膜联蛋白 A11 IgG4 … 随后的无标记定量液相色谱-串联质谱分析和免疫沉淀将胞质蛋白膜联蛋白 A11 确定为靶标。膜联蛋白 A11 IgG4 … 随后的无标记定量液相色谱-串联质谱分析和免疫沉淀将胞质蛋白膜联蛋白 A11 确定为靶标。膜联蛋白 A11 IgG4 …