Arias-Intriago Marlon, Gomolin Tamar, Jaramillo Flor, Cruz-Enríquez Adriana C, Lara-Arteaga Angie L, Tello-De-la-Torre Andrea, Ortiz-Prado Esteban, Izquierdo-Condoy Juan S
One Health Research Group, Universidad de las Américas, Quito 170124, Ecuador.
Department of Pathology, Icahn School of Medicine at Mount Sinai West, New York, NY 10019, USA.
Int J Mol Sci. 2025 Jun 1;26(11):5325. doi: 10.3390/ijms26115325.
Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by tumefactive lesions, IgG4+ plasma cell-rich infiltrates, storiform fibrosis, and obliterative phlebitis. Its multisystem involvement and overlap with malignancies, infections, and immune disorders complicate diagnosis despite recent classification advances. This study summarizes diagnostic challenges, highlights the role of histopathology as per the 2019 classification criteria established by the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR), and explores emerging tools to improve diagnostic accuracy. ACR/EULAR classification emphasizes three cardinal histopathological features (storiform fibrosis, obliterative phlebitis, or dense lymphoplasmacytic infiltrates) combined with an IgG4+/IgG+ plasma cell ratio >40% and organ-specific IgG4+ thresholds. While serum IgG4 levels are often elevated, their poor specificity necessitates confirmatory biopsy. Diagnostic limitations include sampling variability due to patchy fibrosis, interobserver discrepancies in immunohistochemical interpretation, and differentiation from mimics like lymphoma. Emerging solutions incorporate novel biomarkers (plasmablasts, anti-annexin A11) and advanced techniques (flow cytometry, digital pathology). Future research directions should focus on AI-assisted pattern recognition, multi-omics profiling, and organ-specific criteria refinement. While histopathology remains the diagnostic cornerstone, a multidisciplinary approach integrating clinical, radiological, and laboratory data is vital. Innovations in biomarkers promise improved diagnostic accuracy and personalized care, balancing novel advancements with foundational pathological evaluation.
免疫球蛋白G4相关疾病（IgG4-RD）是一种全身性纤维炎症性疾病，其特征为肿块样病变、富含IgG4+浆细胞的浸润、席纹状纤维化和闭塞性静脉炎。尽管近年来在分类方面取得了进展，但其多系统受累以及与恶性肿瘤、感染和免疫紊乱的重叠使得诊断变得复杂。本研究总结了诊断挑战，强调了根据美国风湿病学会和欧洲抗风湿病联盟（ACR/EULAR）制定的2019年分类标准组织病理学的作用，并探索提高诊断准确性的新兴工具。ACR/EULAR分类强调三个主要组织病理学特征（席纹状纤维化、闭塞性静脉炎或密集的淋巴细胞浆细胞浸润），同时结合IgG4+/IgG+浆细胞比例>40%和器官特异性IgG4+阈值。虽然血清IgG4水平通常会升高，但其特异性较差，因此需要进行确诊性活检。诊断局限性包括由于斑片状纤维化导致的采样变异性、免疫组化解释中的观察者间差异以及与淋巴瘤等类似疾病的鉴别。新兴的解决方案包括新型生物标志物（浆母细胞、抗膜联蛋白A11）和先进技术（流式细胞术、数字病理学）。未来的研究方向应集中在人工智能辅助的模式识别、多组学分析以及器官特异性标准的完善。虽然组织病理学仍然是诊断的基石，但整合临床、放射学和实验室数据的多学科方法至关重要。生物标志物的创新有望提高诊断准确性和个性化医疗，在新进展与基础病理学评估之间取得平衡。
