Furube Atsuki, Kadota Tsukasa, Gochi Mina, Saito Susumu, Shibata Shun, Inaki Shunsuke, Tone Kazuya, Takagi Masamichi, Matsuno Hiromasa, Araya Jun, Yaguchi Hiroshi, Kuwano Kazuyoshi
Department of Respiratory Medicine, The Jikei University Kashiwa Hospital, Chiba 277-8567, Japan.
Department of Respiratory Medicine, The Jikei University Kashiwa Hospital, Chiba 277-8567, Japan; Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
Respir Investig. 2022 Sep;60(5):684-693. doi: 10.1016/j.resinv.2022.06.008. Epub 2022 Jul 20.
Anti-aquaporin-4 (AQP4) antibody is an autoantibody marker often observed in patients with neuromyelitis optica spectrum disorder (NMOSD). The pathological relevance of complicated pulmonary disorders in anti-AQP4 antibody-positive NMOSD remains unclear. We aimed to assess the clinical and histological relevance of complicated pulmonary disorders in anti-AQP4 antibody-positive NMOSD.
We retrospectively reviewed the medical records of 52 patients with anti-AQP4 antibody-positive NMOSD and conducted immunohistochemical evaluations of the lung biopsy specimens.
Among 52 patients with anti-AQP4 antibody-positive NMOSD, 4 patients showed pulmonary involvement with a diagnosis of organizing pneumonia (OP). The proportion of males was larger (75% vs. 12.5%; p = 0.013) and creatine kinase levels were higher (458.3 U/L vs. 83.9 U/L; p = 0.003) in patients with OP than in those without OP. OP development preceded or coincided with the NMOSD symptoms. Chest computed tomography findings were consistent with OP in all four patients. Bronchoalveolar lavage fluid predominantly contained lymphocytes. Transbronchial lung biopsy revealed intraluminal plugs of inflammatory debris within the alveoli. Alveolar epithelial cells covering the OP lesions exhibited AQP4 loss, immunoglobulin G deposition, and complement activation. Corticosteroid treatment resulted in clinical improvement of OP.
OP may be considered a pulmonary manifestation of anti-AQP4 antibody-positive NMOSD beyond the central nervous system. Complement-dependent cytotoxicity of the lung epithelial cells caused by anti-AQP4 antibody is at least partly involved in OP development. When diagnosing NMOSD, the possibility of OP should be carefully evaluated based on the detailed history and chest imaging findings.
抗水通道蛋白4（AQP4）抗体是视神经脊髓炎谱系障碍（NMOSD）患者中常观察到的自身抗体标志物。抗AQP4抗体阳性的NMOSD患者并发肺部疾病的病理相关性仍不清楚。我们旨在评估抗AQP4抗体阳性的NMOSD患者并发肺部疾病的临床和组织学相关性。
我们回顾性分析了52例抗AQP4抗体阳性的NMOSD患者的病历，并对肺活检标本进行了免疫组织化学评估。
在52例抗AQP4抗体阳性的NMOSD患者中，4例出现肺部受累，诊断为机化性肺炎（OP）。与无OP的患者相比，OP患者中男性比例更高（75%对12.5%；p = 0.013），肌酸激酶水平更高（458.3 U/L对83.9 U/L；p = 0.003）。OP的发生先于或与NMOSD症状同时出现。所有4例患者的胸部计算机断层扫描结果均与OP一致。支气管肺泡灌洗液中主要含有淋巴细胞。经支气管肺活检显示肺泡腔内有炎性碎屑栓子。覆盖OP病变的肺泡上皮细胞表现出AQP4缺失、免疫球蛋白G沉积和补体激活。皮质类固醇治疗使OP的临床症状得到改善。
OP可能被认为是抗AQP4抗体阳性的NMOSD在中枢神经系统以外的肺部表现。抗AQP4抗体引起的肺上皮细胞补体依赖性细胞毒性至少部分参与了OP的发生。在诊断NMOSD时，应根据详细病史和胸部影像学检查结果仔细评估OP的可能性。
