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Anti-Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency
Aristine Cheng1, Anuj Kashyap1, Helene Salvator1
1From 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.).
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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