Strong April, Sun Ying, Pilcher David, Kaplan Zane, Stirling Rob G
Department of Respiratory Medicine Alfred Health Melbourne Victoria Australia.
Intensive Care Unit Alfred Health Melbourne Victoria Australia.
Respirol Case Rep. 2025 Jun 18;13(6):e70246. doi: 10.1002/rcr2.70246. eCollection 2025 Jun.
Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by circulating anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies that impair alveolar macrophage and neutrophil function. Macrophage dysfunction leads to accumulation of protein- and lipid-rich surfactant within alveoli, impairing gas exchange and leading to respiratory failure. Standard treatments include whole lung lavage (WLL) as first-line therapy, nebulised replacement of GM-CSF, and in refractory cases, lymphocyte depletion, immunosuppression, or lung transplantation. We present a case of a 51-year-old patient with severe, treatment-refractory aPAP failing all standard PAP therapies. A compassionate access program enabled commencement of Daratumumab, a CD38-directed monoclonal antibody (mAb), targeting long-lived plasma cells and providing a novel approach to treatment-resistant autoimmune conditions. One year post completion of Daratumumab, the patient remained in remission with clinical and radiological improvement. There was a corresponding reduction in anti-GM-CSF antibody levels and improvement in gas exchange on pulmonary function testing.
自身免疫性肺泡蛋白沉积症（aPAP）由循环中的抗粒细胞巨噬细胞集落刺激因子（GM-CSF）自身抗体引起，这些抗体损害肺泡巨噬细胞和中性粒细胞功能。巨噬细胞功能障碍导致富含蛋白质和脂质的表面活性物质在肺泡内积聚，损害气体交换并导致呼吸衰竭。标准治疗包括全肺灌洗（WLL）作为一线治疗、雾化吸入GM-CSF替代治疗，以及在难治性病例中进行淋巴细胞清除、免疫抑制或肺移植。我们报告一例51岁患有严重、治疗难治性aPAP的患者，其所有标准PAP治疗均失败。一项同情用药计划使患者能够开始使用达雷妥尤单抗，这是一种靶向CD38的单克隆抗体（mAb），可靶向长寿浆细胞，为治疗耐药的自身免疫性疾病提供了一种新方法。达雷妥尤单抗治疗结束一年后，患者仍处于缓解期，临床和影像学均有改善。抗GM-CSF抗体水平相应降低，肺功能测试显示气体交换有所改善。
