美国加州大学洛杉矶分校Manish J. Butte团队探讨了干扰素-γ联合dupilumab治疗散播性球孢子菌病的疗效。2020年6月11日出版的《新英格兰医学杂志》发表了这项成果。

研究组描述了一个原先健康的儿童发生危及生命的散播性球孢子菌病病例。像大多数散播性球孢子菌病患者一样，这个孩子没有任何已知的罕见免疫疾病的基因组证据。但全面的免疫学测试显示白细胞介素-4生成过多，而干扰素-γ生成减少。

干扰素-γ联合抗真菌药治疗可减缓疾病进展，再加上dupilumab对IL-4和IL-13的阻滞作用可快速缓解患者的临床症状。研究结果显示，阻断2型免疫反应可以治疗感染。这种免疫调节方法可用于增强难治性真菌、分枝杆菌和病毒感染的免疫清除率。

附：英文原文

Title: Disseminated Coccidioidomycosis Treated with Interferon-γ and Dupilumab

Author: Monica Tsai, M.D.,, Timothy J. Thauland, Ph.D.,, Alden Y. Huang, Ph.D.,, Chantana Bun, B.S.,, Sean Fitzwater, M.D.,, Paul Krogstad, M.D.,, Emilie D. Douine, M.S.,, Stanley F. Nelson, M.D.,, Hane Lee, Ph.D.,, Maria I. Garcia-Lloret, M.D.,, and Manish J. Butte, M.D., Ph.D.

Issue&Volume: 2020-06-10

Abstract: Summary We describe a case of life-threatening disseminated coccidioidomycosis in a previously healthy child. Like most patients with disseminated coccidioidomycosis, this child had no genomic evidence of any known, rare immune disease. However, comprehensive immunologic testing showed exaggerated production of interleukin-4 and reduced production of interferon-γ. Supplementation of antifungal agents with interferon-γ treatment slowed disease progression, and the addition of interleukin-4 and interleukin-13 blockade with dupilumab resulted in rapid resolution of the patient’s clinical symptoms. This report shows that blocking of type 2 immune responses can treat infection. This immunomodulatory approach could be used to enhance immune clearance of refractory fungal, mycobacterial, and viral infections.

DOI: 10.1056/NEJMoa2000024

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2000024