Anti–Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency

Abstract

BackgroundAutoantibodies 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.MethodsAmong 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.ResultsAmong 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.ConclusionsAmong 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.)