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Cheng, Aristine; Kashyap, Anuj; Salvator, Helene; Rosen, Lindsey B; Colby, Devon; Ardeshir-Larijani, Fatemeh; Loehrer, Patrick J; Ding, Li; Lugo Reyes, Saul O; Riminton, Sean; Ballman, Madison; Rocco, Joseph M; Marciano, Beatriz E; Freeman, Alexandra F; Browne, Sarah K; Hsu, Amy P; Zelazny, Adrian; Rajan, Arun; Sereti, Irini; Zerbe, Christa S; Lionakis, Michail S; Holland, Steven M
The New England journal of medicine, 2024-Mar-21, Letnik: 390, Številka: 12Journal Article
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. 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. 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. 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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