IgG4 相关性疾病的诊疗研究现状

Recent progress in the diagnosis and management of IgG4-related diseases

摘要

IgG4 相关性疾病 (IgG4-RD) 是一种全身性自身免疫性疾病, 主要特征是慢性炎症和纤维化改变, IgG4-RD 的病因和发病机制尚未完全阐明, 可能与炎症因子、细胞免疫及肠道菌群失调等有关, 需要结合血清学改变、影像学表现和症状等综合分析后诊断, 该疾病治疗手段主要包括糖皮质激素治疗、免疫抑制剂、抗体靶向治疗、调节肠道菌群以及药物联合治疗等。本文旨在阐述 IgG4-RD 的发病机制、临床症状、诊疗方案的研究进展, 为 IgG4-RD 的临床诊疗提供新思路。

Abstract

IgG4-related disease (IgG4-RD) is a systemic autoimmune disorder condition largely distinguished by persistent inflammation and fibrotic alterations. The etiology and pathogenesis of IgG4-RD are not fully elucidated but may involve inflammatory mediators, cellular immunity, and dysbiosis of the gut microbiota. Diagnosis necessitates a thorough evaluation of serological alterations, imaging results, and clinical manifestations. This disease can impact several organs and tissues, with clinical presentations classified into systemic symptoms, organ-specific symptoms, and mass-like lesions. Treatment modalities encompass glucocorticoids, immunosuppressants, antibody-targeted treatments, modification of gut microbiota, and prospective combination medicines. This article is to examine recent developments in the pathophysiology, clinical symptoms, diagnosis, and treatment approaches of IgG4-RD, offering fresh perspectives for future clinical management.

关键词

IgG4 相关性疾病 / 发病机制 / 诊疗进展 / 研究现状

Key words

IgG4-related diseases / Pathogenesis / Advances in diagnosis and treatment / Current state of research

参考文献

[1] 张文, 董凌莉, 朱剑, 等 . IgG4 相关性疾病诊治中国专家共识[J]. 中华内科杂志, 2021, 60(3): 192-206.

[2] Zhang W, Dong L L, Zhu J, et al. Chinese expert consensus on the diagnosis and treatment of IgG4 related diseases[J]. Chin J Intern Med, 2021, 60(3): 192-206.

[3] Koike T . IgG4—related disease: why high IgG4 and fibrosis? [J]. Arthritis Res Ther, 2013, 15(1): 103.

[4] Kawano M . IgG4—related disease: recent topics on immunological aspects of this disorder and their application in new treatment strategies[J]. Intern Med, 2025, 64(1): 31-39.

[5] Haoyan Y, Yanran, Jian Y, et al. Advances in the pathogenesis and targeted therapy of IgG4—related diseases[J]. Chin J Rheumatol, 2024, 28(9): 693-696.

[6] Aoyagi R, Maehara T, Koga R, et al. Single—cell transcriptomics reveals granzyme K—expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4—RD [J]. J Allergy Clin Immunol, 2024, 153(2): 513-520.e10.

[7] Martín—Nares E, Hernández—Molina G, Priego—Ranero Á A, et al. Peripheral immunophenotype in IgG4—related disease and its association with clinical phenotypes and disease activity[J]. Cells, 2023, 12(4): 670.

[8] 任婷婷, 李静, 马建民 . IgG4 相关性疾病肠道微生物组学的研究进展[J]. 中国医师杂志, 2024, 26(11): 1748-1752.

[9] Ren T T, Li J, Ma J M. Advances in gut microbiomes of IgG4—associated diseases[J]. J Chin Physician, 2024, 26(11): 1748-1752.

[10] Pan X X, Wu Z W . Advances in gut microbiomes and immunology of IgG4—related hepatobiliary and pancreatic diseases[J]. Zhonghua Gan Zang Bing Za Zhi, 2022, 30(4): 452-456.

[11] Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4—related disease (IgG4—RD), 2011[J]. Mod Rheumatol, 2012, 22(1): 21-30.

[12] 嵇金陵, 姜玉章, 韩崇旭, 等 . 不同血清 IgG4 临界值对 IgG4 相关性疾病的诊断效能[J]. 检验医学, 2024, 39(8): 733-737.

[13] Ji J L, Jiang Y Z, Han C X, et al. Diagnostic efficacy of different serum IgG4 thresholds for IgG4—related diseases[J]. Lab Med, 2024, 39(8): 733-737.

[14] Zhao E J, Carruthers M N, Li C H, et al. Conditions associated with polyclonal hypergammaglobulinemia in the IgG4—related disease era: a retrospective study from a hematology tertiary care center[J]. Haematologica, 2020, 105(3): e121-e123.

[15] 夏雨鑫, 姜玉章 . IgG4 相关性疾病潜在生物学标志物的研究进展[J]. 临床检验杂志, 2023, 41(8): 614-617.

[16] Xia Y X, Jiang Y Z. Research progress on potential biomarkers of IgG4—related diseases [J]. Chin J clin Lab Sci, 2023, 41(8): 614-617.

[17] Zhou J, Peng Y, Peng L, et al. Serum IgE in the clinical features and disease outcomes of IgG4—related disease: a large retrospective cohort study[J]. Arthritis Res Ther, 2020, 22(1): 255.

[18] Löhr J M, Vujasinovic M, Rosendahl J, et al. IgG4—related diseases of the digestive tract[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(3): 185-197.

[19] Wallace Z S, Naden R P, Chari S, et al. The 2019 American College of Rheumatology/ European League Against Rheumatism Classification Criteria for IgG4—Related Disease[J]. Arthritis Rheumatol, 2020, 72(1): 7-19.

[20] 周玮, 沈伟强, 沈博, 等 . IgG4 相关硬化性胆管炎的临床特征及影像学表现[J]. 医学影像学杂志, 2022, 32(8): 1323-1327.

[21] Zhou W, Shen W Q, Shen B, et al. Clinical and imaging features of immunoglobulin G4—related sclerosing cholangitis[J]. J Med Imaging, 2022, 32(8): 1323-1327.

[22] Tanaka A, Tazuma S, Okazaki K, et al. Clinical features, response to treatment, and outcomes of IgG4—related sclerosing cholangitis[J]. Clin Gastroenterol Hepatol, 2017, 15(6): 920-926.e3.

[23] Wu S, Wang H . IgG4—related digestive diseases: diagnosis and treatment [J]. Front Immunol, 2023, 14: 1278332.

[24] Nakazawa T, Kamisawa T, Okazaki K, et al. Clinical diagnostic criteria for IgG4—related sclerosing cholangitis 2020: (Revision of the clinical diagnostic criteria for IgG4—related sclerosing cholangitis 2012)[J]. J Hepatobiliary Pancreat Sci, 2021, 28(3): 235-242.

[25] 郭长存, 时永全, 尚玉龙, 等 . 原发性硬化性胆管炎诊断及治疗指南(2021) [J]. 临床肝胆病杂志, 2022, 38(1): 50-61.

[26] Guo C C, Shi Y Q, Shang Y L, et al. Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021)[J]. J Clin Hepatol, 2022, 38(1): 50-61.

[27] Saeki T, Nishi S, Imai N, et al. Clinicopathological characteristics of patients with IgG4—related tubulointerstitial nephritis[J]. Kidney Int, 2010, 78(10): 1016-1023.

[28] Chaba A, Devresse A, Audard V, et al. Clinical and prognostic factors in patients with IgG4—related kidney disease[J]. Clin J Am Soc Nephrol, 2023, 18(8): 1031-1040.

[29] 李琪, 王悦 . 血清主导的及肾小球沉积的 IgG 亚型和补体分子对肾小球疾病作用的研究进展[J]. 临床肾脏病杂志, 2024, 24(7): 598-602.

[30] LI Q, Wang Y. Research advances on the effects of serum—dominated and glomerular deposited IgG subclasses and complement molecules on glomerular diseases[J]. J Clin Nephrol, 2024, 24(7): 598-602.

[31] 姜超, 吴哲, 孙露露, 等 . IgG4 相关性肾病累及肾盂的 CT 影像表现 [J]. 放射学实践, 2021, 36(11): 1414-1418.

[32] Jiang C, Wu Z, Sun L L, et al. CT imaging findings of IgG4—related kidney disease with renal pelvic involvement[J]. Radiol Pract, 2021, 36(11): 1414-1418.

[33] 刘屹霄, 杨莹韵, 杨爱明 . Ⅰ型自身免疫性胰腺炎发病机制及研究进展[J]. 协和医学杂志, 2023, 14(4): 826-832.

[34] Liu Y X, Yang Y Y, Yang A M. Advances in the pathogenesis of type Ⅰ autoimmune pancreatitis [J]. Med J Peking Union Med Coll Hosp, 2023, 14(4): 826-832.

[35] Masamune A, Kikuta K, Hamada S, et al. Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016 [J]. J Gastroenterol, 2020, 55(4): 462-470.

[36] Khandelwal A, Inoue D, Takahashi N . Autoimmune pancreatitis: an update [J]. Abdom Radiol (NY), 2020, 45(5): 1359-1370.

[37] 赵瑞敏, 王小月, 张惠霞 . 血清 CA19—9、TAP、IgG4 联合检测在 IgG4 相关性自身免疫性胰腺炎与胰腺癌鉴别诊断中的临床价值分析[J]. 肿瘤基础与临床, 2022, 35(2): 136-140.

[38] Zhao R M, Wang X Y, Zhang H X. Clinical value of combined detection of serum CA19—9,TAP and IgG4 in the differential diagnosis of IgG4—related autoimmune pancreatitis and pancreatic cancer[J]. J Basic and Clin Oncol, 2022, 35(2): 136-140.

[39] 王天琪, 刘燕鹰 . IgG4 相关肝胆胰疾病诊疗进展[J]. 临床肝胆病杂志, 2022, 38(4): 762-766.

[40] Wang T Q, Liu Y Y. Advances in diagnosis and treatment of IgG4—related hepatobiliary and pancreatic diseases[J]. J Clin Hepatol, 2022, 38(4): 762-766.

[41] Uchida K, Okazaki K . Current status of type 1 (IgG4—related) autoimmune pancreatitis [J]. J Gastroenterol, 2022, 57(10): 695-708.

[42] Goldoni M, Bonini S, Urban M L, et al. Asbestos and smoking as risk factors for idiopathic retroperitoneal fibrosis: a case—control study[J]. Ann Intern Med, 2014, 161(3): 181-188.

[43] Chao Y, Li R, Shao Y, et al. Factors associated with early clinical remission in patients with idiopathic retroperitoneal fibrosis[J]. Rheumatology (Oxford), 2024:keae676 [pii].

[44] Simshon—Turgeman M, Rosenberg E, Bartal A, et al. Asymptomatic testicular tumor in patient with retroperitoneal fibrosis as manifestation of IgG4—related disease recurrence: a case report [J]. Isr Med Assoc J, 2024, 26(10): 655-657.

[45] Ji X, Zhang Z, Du F, et al. Successful transcolonic endoscopic ultrasound—guided fine—needle biopsy of retroperitoneal fibrosis [J]. Endoscopy, 2025, 57(S 01): E133-E134.

[46] Erickson R A, Tretjak Z . Clinical utility of endoscopic ultrasound and endscopic ultrasound—guided fine needle aspiration in retroperitoneal neoplasms[J]. Am J Gastroenterol, 2000, 95(5): 1188-1194.

[47] Hu J Q, Jin Z Y, Yu Y Y, et al. Clinical characteristics of IgG4—related retroperitoneal fibrosis in a cohort of 117 patients with idiopathic retroperitoneal fibrosis: a retrospective study [J]. Clin Rheumatol, 2025, 44(2): 757-766.

[48] 闫俊, 朱葛敏, 高亚亚, 等 . 甲氨蝶呤联合甲泼尼龙对老年类风湿关节炎患者脑白质疏松的影响[J]. 国际老年医学杂志, 2023, 44(1): 53-56.

[49] Yan J, Zhu G M, Gao Y Y, et al. Effect of methotrexate combined with methylprednisolone on leukoaraiosis in older patients with rheumatoid arthritis[J]. Int J Geriatr, 2023, 44(1): 53-56.

[50] Okazaki K, Kawa S, Kamisawa T, et al. Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020[J]. J Gastroenterol, 2022, 57(4): 225-245.

[51] 郑岷敏, 聂玉雪, 张文 . IgG4 相关性疾病药物治疗进展[J]. 中国新药杂志, 2022, 31(23): 2296-2303.

[52] Zheng M M, Nie Y X, Zhang W. Advances in drug therapy for IgG4—related diseases[J]. Chin J New Drug, 2022, 31(23): 2296-2303.

[53] Omar D, Chen Y, Cong Y, et al. Glucocorticoids and steroid sparing medications monotherapies or in combination for IgG4—RD: a systematic review and network meta—analysis[J]. Rheumatology (Oxford), 2020, 59(4): 718-726.

[54] 彭琳一, 聂玉雪, 费允云, 等 . 稳定期 IgG4 相关性疾病患者减停药策略的研究[J]. 罕见病研究, 2024, 3(3): 326-328.

[55] Peng L Y, Nie Y X, Fei Y Y, et al. Withdrawal of immunosuppressants and low—dose steroids in patients with stable IgG4—RD[J]. J Race Dis, 2024, 3(3): 326-328.

[56] Lanzillotta M, Mancuso G, Della—Torre E . Advances in the diagnosis and management of IgG4 related disease[J]. BMJ, 2020, 369: m1067.

[57] Carruthers M N, Topazian M D, Khosroshahi A, et al. Rituximab for IgG4—related disease: a prospective, open—label trial [J]. Ann Rheum Dis, 2015, 74(6): 1171-1177.

[58] Campochiaro C, Della—Torre E, Lanzillotta M, et al. Long—term efficacy of maintenance therapy with Rituximab for IgG4—related disease [J]. Eur J Intern Med, 2020, 74: 92-98.

[59] Löhr J M, Beuers U, Vujasinovic M, et al. European guideline on IgG4—related digestive disease — UEG and SGF evidence—based recommendations[J]. United European Gastroenterol J, 2020, 8(6): 637-666.

[60] Peyronel F, Vaglio A . IgG4—related kidney disease[J]. Clin J Am Soc Nephrol, 2023, 18(8): 994-996.