抗白细胞介素-23 自身抗体在成人发病免疫缺陷中的作用。
Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency.
机构信息
From the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (A.C., A.K., H.S., L.B.R., D.C., L.D., J.M.R., B.E.M., A.F.F., S.K.B., A.P.H., A.Z., I.S., C.S.Z., M.S.L., S.M.H.), and the Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute (M.B., A.R.), National Institutes of Health, Bethesda, MD; the Division of Infectious Diseases, Department of Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (A.C.); the Department of Respiratory Medicine, Hôpital Foch, Unité Mixte de Recherche 0892, Virology and Molecular Immunology Laboratory, Suresnes Paris-Saclay University, Suresnes, France (H.S.); Indiana University Melvin and Bren Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis (F.A.-L., P.J.L.); Immune Deficiencies Laboratory, National Institute of Pediatrics, Mexico City (S.O.L.R.); and the Department of Immunology, Repatriation General Hospital Concord, University of Sydney, Concord, NSW, Australia (S.R.).
出版信息
N Engl J Med. 2024 Mar 21;390(12):1105-1117. doi: 10.1056/NEJMoa2210665.
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 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 and 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.).
背景
自身免疫性抗体针对白细胞介素-12（抗白细胞介素-12）通常在胸腺瘤患者中被发现，但这些患者中只有一部分发生机会性感染。白细胞介素-12（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。在一位患有播散性感染的患者中，识别抗白细胞介素-23 和抗白细胞介素-12 促使进一步调查。
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，我们筛选了针对白细胞介素-23 的自身抗体（抗白细胞介素-23）。为了验证抗白细胞介素-23 对机会性感染的潜在作用，我们还测试了第二组胸腺瘤患者以及既没有胸腺瘤也没有已知抗白细胞介素-12 的但有不寻常感染的患者。
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，有 15 名（50%）患者也存在中和白细胞介素-23 的自身抗体。这种中和的效力与这些感染的严重程度相关。单独的抗白细胞介素-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，在 74 名患者（81%）中，抗白细胞介素-23 的存在与感染状态相关。总的来说，在 116 名胸腺瘤患者中有 30 名（26%）和在 36 名播散性、脑或肺部感染患者中有 30 名（83%）检测到中和抗白细胞介素-23。在 32 名严重细胞内感染患者中有 6 名（19%）和 16 名颅内感染患者中有 2 名（12%）患者（包括 和 复杂）中发现了抗白细胞介素-23。
结论
在各种分枝杆菌、细菌或真菌感染患者中，存在中和抗白细胞介素-23 与严重、持续的机会性感染有关。（由美国国立过敏和传染病研究所和其他机构资助）。
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