Division of Pediatric Rheumatology, Medical College Wisconsin, Milwaukee, Wis; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis.
Asthma, Allergy and Clinical Immunology, Children's Wisconsin, Milwaukee, Wis.
J Allergy Clin Immunol. 2021 Feb;147(2):704-712.e17. doi: 10.1016/j.jaci.2020.07.021. Epub 2020 Aug 1.
Granulomatous and lymphocytic interstitial lung disease (GLILD) is a life-threatening complication in patients with common variable immunodeficiency (CVID), but the optimal treatment is unknown.
Our aim was to determine whether rituximab with azathioprine or mycophenolate mofetil improves the high-resolution computed tomography (HRCT) chest scans and/or pulmonary function test results in patients with CVID and GLILD.
A retrospective chart review of clinical and laboratory data on 39 patients with CVID and GLILD who completed immunosuppressive therapy was performed. Chest HRCT scans, performed before therapy and after the conclusion of therapy, were blinded, randomized, and scored independently by 2 radiologists. Differences between pretreatment and posttreatment HRCT scan scores, pulmonary function test results, and lymphocyte subsets were analyzed. Whole exome sequencing was performed on all patients.
Immunosuppressive therapy improved patients' HRCT scan scores (P < .0001), forced vital capacity (P = .0017), FEV (P = .037), and total lung capacity (P = .013) but not their lung carbon monoxide diffusion capacity (P = .12). Nine patients relapsed and 6 completed retreatment, with 5 of 6 of these patients (83%) having improved HRCT scan scores (P = .063). Relapse was associated with an increased number of B cells (P = .016) and activated CD4 T cells (P = .016). Four patients (10%) had pneumonia while undergoing active treatment, and 2 patients (5%) died after completion of therapy. Eight patients (21%) had a damaging mutation in a gene known to predispose (TNFRSF13B [n = 3]) or cause a CVID-like primary immunodeficiency (CTLA4 [n = 2], KMT2D [n = 2], or BIRC4 [n = 1]). Immunosuppression improved the HRCT scan scores in patients with (P = .0078) and without (P < .0001) a damaging mutation.
Immunosuppressive therapy improved the radiographic abnormalities and pulmonary function of patients with GLILD. A majority of patients had sustained remissions.
肉芽肿性和淋巴细胞性间质性肺病（GLILD）是普通变异性免疫缺陷（CVID）患者的一种危及生命的并发症，但最佳治疗方法尚不清楚。
我们旨在确定利妥昔单抗联合硫唑嘌呤或霉酚酸酯是否能改善 CVID 合并 GLILD 患者的高分辨率计算机断层扫描（HRCT）胸部扫描和/或肺功能检查结果。
对 39 例接受免疫抑制治疗的 CVID 合并 GLILD 患者的临床和实验室数据进行回顾性图表分析。在治疗前和治疗结束后进行胸部 HRCT 扫描，由 2 名放射科医生进行盲法、随机和独立评分。分析治疗前后 HRCT 扫描评分、肺功能检查结果和淋巴细胞亚群的差异。对所有患者进行全外显子组测序。
免疫抑制治疗改善了患者的 HRCT 扫描评分（P<0.0001）、用力肺活量（P=0.0017）、FEV1（P=0.037）和总肺活量（P=0.013），但不包括肺一氧化碳弥散量（P=0.12）。9 例患者复发，6 例完成再治疗，其中 6 例中的 5 例（83%）HRCT 扫描评分改善（P=0.063）。复发与 B 细胞数量增加（P=0.016）和活化 CD4 T 细胞数量增加（P=0.016）相关。4 例（10%）患者在接受积极治疗时发生肺炎，2 例（5%）患者在治疗结束后死亡。8 例（21%）患者在已知易患（TNFRSF13B[3 例]）或引起 CVID 样原发性免疫缺陷（CTLA4[2 例]、KMT2D[2 例]或 BIRC4[1 例]）的基因中存在破坏性突变。免疫抑制治疗改善了有（P=0.0078）和无（P<0.0001）破坏性突变患者的 HRCT 扫描评分。
免疫抑制治疗改善了 GLILD 患者的影像学异常和肺功能。大多数患者有持续缓解。
