普通变异型免疫缺陷病相关间质性肺病：发病机制、诊断挑战与治疗策略

Interstitial Lung Disease Associated with Common Variable Immunodeficiency: Pathogenesis, Diagnostic Challenges, and Therapeutic Strategies

摘要: 普通变异型免疫缺陷病(CVID)是一类以抗体生成障碍为核心表征的免疫缺陷疾病，低丙种球蛋白血症为其典型特征。CVID临床表现具有高度异质性，涵盖反复感染、自身免疫现象、炎症性并发症以及淋巴组织增生等多种情况。其中，CVID相关间质性肺病(CVID-ILD)已成为CVID最重要的非感染性并发症之一。尽管CVID-ILD的确切发病机制尚未完全阐明，但目前研究普遍认为免疫失调和肺部感染是其主要诱因，免疫调节异常、B细胞功能缺陷以及T细胞活化在其发病进程中发挥重要作用。现阶段，CVID-ILD的诊断依赖于影像学、临床症状以及实验室检查等多维度的综合分析。在此过程中，肺部影像学检查在CVID-ILD的诊断与疾病进展评估中占据关键地位。肺部高分辨率CT下，CVID-ILD呈现出磨玻璃样混浊、弥漫性结节、淋巴结肿大等典型影像学特征。虽然当前CVID-ILD诊断缺乏特异性生物标志物，但部分生物标志物，如B细胞激活因子(BAFF)和白细胞介素-2受体(IL-2R)，在疾病的诊断与病情监测方面展现出潜在的应用价值。治疗策略方面，传统的CVID-ILD治疗方案为免疫球蛋白替代治疗联合免疫抑制剂应用。而生物制剂(如利妥昔单抗和阿巴西普)的应用，使CVID-ILD治疗取得显著进展，能有效提升患者的临床缓解率，改善肺功能。本文对CVID-ILD的发病机制、影像学特征、生物标志物、治疗策略以及预后情况进行全面综述，旨在为临床诊疗提供理论基础与实践指导。

Abstract: Common variable immunodeficiency disease (CVID) is a class of immunodeficiency diseases characterized by impaired antibody production, and hypogammaglobulinemia is its typical feature. The clinical manifestations of CVID are highly heterogeneous, encompassing a variety of conditions including recurrent infections, autoimmune phenomena, inflammatory complications, and lymphoproliferation. Among them, CVID-associated interstitial lung disease (CVID-ILD) has emerged as one of the most important non-infectious complications of CVID. Although the exact pathogenesis of CVID-ILD has not been fully elucidated, it is generally accepted that immune dysregulation and pulmonary infection are the main causes, with abnormal immune regulation, defective B cell function, and T cell activation playing an important role in its pathogenesis. At present, the diagnosis of CVID-ILD relies on multi-dimensional comprehensive analysis, such as imaging, clinical symptoms, and laboratory tests. In this process, lung imaging plays a key role in the diagnosis of CVID-ILD and the assessment of disease progression. On high-resolution CT of the lungs, CVID-ILD shows typical imaging features, such as ground-glass opacities, diffuse nodules, and lymphadenopathy. Although there is a lack of specific biomarkers for the diagnosis of CVID-ILD, some biomarkers, such as B-cell activator (BAFF) and interleukin-2 receptor (IL-2R), have shown potential applications in the diagnosis and monitoring of diseases. In terms of treatment strategy, the traditional CVID-ILD regimen is immunoglobulin replacement therapy combined with immunosuppressive therapy. The use of biologics (such as rituximab and abatacept) has led to significant progress in the treatment of CVID-ILD, which can effectively improve the clinical response rate and improve lung function of patients. This article reviews the pathogenesis, imaging features, biomarkers, treatment strategies, and prognosis of CVID-ILD, aiming to provide theoretical basis and practical guidance for clinical diagnosis and treatment.