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期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2210665

摘要内容如下：

背景

抗白细胞介素-12自身抗体（抗白细胞介素-12）常在胸腺瘤患者中发现，但仅在部分患者中发生机会性感染。白细胞介素-12（具有亚基p40和p35）与白细胞介素-23（亚基p40和P19）共享一个共同的亚基。在一名患有播散性唐菖蒲伯克霍尔德菌感染的患者中，抗白细胞介素-23和抗白细胞介素-12的鉴定促进了进一步的研究。

方法

在已知具有抗白细胞介素-12的患者（其中大多数患有胸腺瘤）中，我们筛选了抗白细胞介素-23的自身抗体（抗白细胞介素-23）。为了验证抗白介素-23抗体在机会性感染中的潜在作用，我们测试了第二组胸腺瘤患者以及无胸腺瘤或已知抗白介素-12抗体但有异常感染的患者。

结果

在30名患有严重分枝杆菌、细菌或真菌感染的抗白细胞介素-12患者中，15名（50%）同时具有中和白细胞介素-23的自身抗体。这种中和作用的效力与这些感染的严重程度相关。单独抗白细胞介素-12的中和活性与感染无关。在91名胸腺瘤患者的验证队列中，74名患者（81%）的抗白细胞介素-23抗体的存在与感染状态相关。总体而言，在116例胸腺瘤患者中有30例（26%）和36例播散性、脑部或肺部感染患者中有30例（83%）检测到中和抗白细胞介素-23。32例严重细胞内感染患者中有6例（19%）存在抗白细胞介素-23抗体，16例罕见颅内感染患者中有2例（12%）存在抗白细胞介素-23抗体，包括斑状刚毛藻和鸟分枝杆菌复合群。

结论

在患有各种分枝杆菌、细菌或真菌感染的患者中，中和性抗白细胞介素-23的存在与严重、持续的机会性感染相关。（由国家过敏和传染病研究所和其他机构资助。）。

英文原文如下：

Abstracts

BACKGROUND  Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation.

METHODS  Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections.

RESULTS  Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex.

CONCLUSIONS  Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

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