Allergy and Clinical Immunology Department, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain.
Functional Unit of Clinical Immunology, Hospital Sant Joan de Déu-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
Pediatr Allergy Immunol. 2018 Jun;29(4):425-432. doi: 10.1111/pai.12890. Epub 2018 Apr 17.
One of the most frequent non-infectious complications of humoral immunodeficiencies with a CVID-like pattern is a particular form of inflammatory lung disease which is called granulomatous-lymphocytic interstitial lung disease (GLILD). Its development worsens patient prognosis, with a significant decrease in survival. Currently, there are no unified guidelines regarding its management, and different combinations of immunosuppressants have been used with variable success.
Clinical and radiological data were collected from patient's medical charts. Flow cytometry was performed to characterize the immunological features with special focus in regulatory T cells (Tregs).
A 16-year-old girl with Kabuki syndrome and a 12-year-old boy, both with a CVID-like humoral immunodeficiency on immunoglobulin replacement treatment, developed during follow-up an inflammatory complication radiologically, clinically, and histologically compatible with GLILD. They required treatment, and sirolimus was started, with very good response and no serious side effects.
These 2 cases provide insight into the underlying local and systemic immune anomalies involved in the development of GLILD, including the possible role of Tregs. Combined chemotherapy is commonly used as treatment for GLILD when steroids fail, but there have been some reports of successful monotherapy. As far as we know, these are the first 2 GLILD patients treated successfully with sirolimus, suggesting the advisability of further study of mTOR inhibitors as a more targeted treatment for GLILD, if impairment in Tregs is demonstrated.
具有 CVID 样模式的体液免疫缺陷的最常见的非传染性并发症之一是一种特殊形式的炎症性肺疾病，称为肉芽肿性淋巴细胞性间质肺病（GLILD）。其发展使患者预后恶化，生存率显著下降。目前，其管理尚无统一的指南，不同免疫抑制剂的组合已被用于不同程度的成功。
从患者的病历中收集临床和放射学数据。进行流式细胞术以描述免疫特征，特别关注调节性 T 细胞（Tregs）。
一名患有歌舞伎综合征的 16 岁女孩和一名 12 岁男孩，均在免疫球蛋白替代治疗下具有 CVID 样体液免疫缺陷，在随访期间出现了一种炎症性并发症，在放射学、临床和组织学上与 GLILD 相符。他们需要治疗，开始使用西罗莫司，反应非常好，没有严重的副作用。
这两个病例深入了解了 GLILD 发展中涉及的局部和全身免疫异常，包括 Tregs 的可能作用。当类固醇治疗失败时，联合化疗通常被用作 GLILD 的治疗方法，但已有一些成功的单药治疗报告。据我们所知，这是首例成功用西罗莫司治疗的 2 例 GLILD 患者，表明如果 Tregs 受损，mTOR 抑制剂作为 GLILD 的更有针对性的治疗方法值得进一步研究。
