Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy.
Eur J Clin Microbiol Infect Dis. 2024 May;43(5):1003-1007. doi: 10.1007/s10096-024-04785-z. Epub 2024 Feb 20.
Infections that are unusually severe or caused by opportunistic pathogens are a hallmark of primary immunodeficiency (PID). Anti-cytokine autoantibodies (ACA) are an emerging cause of acquired immunodeficiency mimicking PID. Nocardia spp. are Gram-positive bacteria generally inducing disseminated infections in immunocompromised patients, but seldom also occurring in apparently immunocompetent hosts. Anti-GM-CSF autoantibodies are associated with autoimmune pulmonary alveolar proteinosis (PAP). In those patients, an increased incidence of disseminated nocardiosis and cryptococcosis has been observed. It is unclear whether the PAP or the autoantibodies predispose to the infection. We report an apparently immunocompetent woman presenting with disseminated nocardiosis without any evidence of PAP. Clinical data and radiological images were retrospectively collected. Lymphocyte populations were analyzed by flow cytometry. Anti-GM-CSF autoantibodies were measured by ELISA. A 55-year-old otherwise healthy woman presented with cerebral and pulmonary abscesses. Personal and familial history of infections or autoimmunity were negative. After extensive examinations, a final diagnosis of disseminated nocardiosis was made. Immunologic investigations including neutrophilic function and IFN-γ/IL-12 circuitry failed to identify a PID. Whole-exome sequencing did not find pathogenic variants associated with immunodeficiency. Serum anti-GM-CSF autoantibodies were positive. There were no clinical or instrumental signs of PAP. Trimethoprim-sulfamethoxazole and imipenem were administered, with progressive improvement and recovery of the infectious complication. We identified anti-GM-CSF autoantibodies as the cause of disseminated nocardiosis in a previously healthy and apparently immunocompetent adult. This case emphasizes the importance of including ACA in the differential diagnosis of PID, especially in previously healthy adults. Importantly, anti-GM-CSF autoantibodies can present with disseminated nocardiosis without PAP.
原发性免疫缺陷（PID）的一个标志是异常严重或由机会性病原体引起的感染。抗细胞因子自身抗体（ACA）是一种新兴的获得性免疫缺陷模拟 PID 的原因。诺卡氏菌属是革兰氏阳性细菌，通常在免疫功能低下的患者中引起播散性感染，但也很少发生在明显免疫功能正常的宿主中。抗 GM-CSF 自身抗体与自身免疫性肺泡蛋白沉积症（PAP）有关。在这些患者中，已观察到播散性诺卡氏菌病和 cryptococcosis 的发病率增加。尚不清楚是 PAP 还是自身抗体导致感染。我们报告了一例明显免疫功能正常的妇女，她患有播散性诺卡氏菌病，没有任何 PAP 的证据。回顾性收集了临床数据和影像学图像。通过流式细胞术分析淋巴细胞群。通过 ELISA 测量抗 GM-CSF 自身抗体。一名 55 岁的健康女性出现脑和肺脓肿。个人和家族感染或自身免疫史均为阴性。经过广泛检查，最终诊断为播散性诺卡氏菌病。包括中性粒细胞功能和 IFN-γ/IL-12 电路在内的免疫研究未能确定 PID。全外显子组测序未发现与免疫缺陷相关的致病性变异。血清抗 GM-CSF 自身抗体阳性。没有 PAP 的临床或仪器迹象。给予甲氧苄啶-磺胺甲恶唑和亚胺培南，感染并发症逐渐改善和恢复。我们确定抗 GM-CSF 自身抗体是先前健康和明显免疫功能正常的成年患者播散性诺卡氏菌病的原因。该病例强调了在 PID 的鉴别诊断中包括 ACA 的重要性，尤其是在先前健康的成年人中。重要的是，抗 GM-CSF 自身抗体可在无 PAP 的情况下出现播散性诺卡氏菌病。
