B Cell Dysregulation in Common Variable Immunodeficiency Interstitial Lung Disease.
B Cell Dysregulation in Common Variable Immunodeficiency Interstitial Lung Disease.
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DOI：
10.3389/fimmu.2020.622114
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发表时间：
2020
影响因子：
7.3
通讯作者：
Maglione PJ
中科院分区：
文献类型：
--
作者：
Matson EM;Abyazi ML;Bell KA;Hayes KM;Maglione PJ
常见变异免疫缺陷（CVID）是最常诊断的一抗缺陷。大约一半的 CVID 患者会出现慢性非感染性并发症，被认为是由于内在免疫失调所致，包括自身免疫、胃肠道疾病和间质性肺疾病 (ILD)。多项研究发现 ILD 是 CVID 发病和死亡的重要原因。然而，人们对 CVID 并发症的确切机制知之甚少。 CVID ILD 的特点是 T 细胞和 B 细胞的深度肺部浸润以及许多病例中的肉芽肿性炎症。 B 细胞耗竭疗法，无论是作为单一疗法还是与另一种免疫抑制剂联合使用，都已成为 CVID ILD 的治疗标准。然而，CVID 是一种异质性疾病，其肺部病理学也是如此，而哪些患者可以从 B 细胞耗竭疗法中受益、何时应该进行治疗以及应该重复治疗多长时间，这些都仍然是我们的知识空白。此外，一些人在 B 细胞消除治疗后出现 ILD 复发，并且 B 细胞生物学的相对重要性仍未完全确定。在 CVID ILD 和相关病症中观察到的 B 细胞区室的发育和功能异常表明，B 细胞信号网络的不平衡可能会促进肺部疾病。这些潜在的疾病机制中包括 B 细胞激活因子 (BAFF)，这是一种由干扰素 γ (IFN-γ):STAT1 信号轴上调的细胞因子，可有效影响 B 细胞的激活和存活。 B 细胞对 BAFF 的反应由其三种受体的不同作用和表达模式决定：BAFF 受体 (BAFF-R)、跨膜激活剂和 CAML 相互作用因子 (TACI) 以及 B 细胞成熟抗原 (BCMA)。此外，BAFF-R、TACI 和 BCMA 的可溶形式存在，可能进一步影响 ILD 的发病机制。继续努力了解 B 细胞生物学失调如何促进 ILD 的发生和进展，将有助于缩小我们对如何最好地诊断、定义和管理 CVID 中 ILD 的理解差距。
Common variable immunodeficiency (CVID) is the most frequently diagnosed primary antibody deficiency. About half of CVID patients develop chronic non-infectious complications thought to be due to intrinsic immune dysregulation, including autoimmunity, gastrointestinal disease, and interstitial lung disease (ILD). Multiple studies have found ILD to be a significant cause of morbidity and mortality in CVID. Yet, the precise mechanisms underlying this complication in CVID are poorly understood. CVID ILD is marked by profound pulmonary infiltration of both T and B cells as well as granulomatous inflammation in many cases. B cell depletive therapy, whether done as a monotherapy or in combination with another immunosuppressive agent, has become a standard of therapy for CVID ILD. However, CVID is a heterogeneous disorder, as is its lung pathology, and the precise patients that would benefit from B cell depletive therapy, when it should administered, and how long it should be repeated all remain gaps in our knowledge. Moreover, some have ILD recurrence after B cell depletive therapy and the relative importance of B cell biology remains incompletely defined. Developmental and functional abnormalities of B cell compartments observed in CVID ILD and related conditions suggest that imbalance of B cell signaling networks may promote lung disease. Included within these potential mechanisms of disease is B cell activating factor (BAFF), a cytokine that is upregulated by the interferon gamma (IFN-γ):STAT1 signaling axis to potently influence B cell activation and survival. B cell responses to BAFF are shaped by the divergent effects and expression patterns of its three receptors: BAFF receptor (BAFF-R), transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA). Moreover, soluble forms of BAFF-R, TACI, and BCMA exist and may further influence the pathogenesis of ILD. Continued efforts to understand how dysregulated B cell biology promotes ILD development and progression will help close the gap in our understanding of how to best diagnose, define, and manage ILD in CVID.
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