Neutralizing anti-interleukin-23 is associated with severe, persistent, opportunistic infections, according to a study published in the March 21 issue of the New England Journal of Medicine.
Noting that interleukin-12 shares a common subunit with interleukin-23, Aristine Cheng, M.D., from the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and colleagues screened patients (most of whom had thymoma) who were known to have anti-interleukin-12 for autoantibodies against interleukin-23. In addition, a second cohort of patients with thymoma and those without thymoma or known anti-interleukin-12 with unusual infections was tested.
The researchers found that 50 percent of the 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections had antibodies that neutralized interleukin-23. There was a correlation noted between the potency of such neutralization and the severity of these infections. There was no association seen for the neutralizing activity of anti-interleukin-12 alone with infection. The presence of anti-interleukin-23 was associated with infection status in 81 percent of the validation cohort of 91 patients with thymoma. Overall, neutralizing anti-interleukin-23 was detected in 26 percent of the patients with thymoma and 83 percent with disseminated, cerebral, or pulmonary infections. In 19 and 12 percent of patients with severe intracellular infections and unusual intracranial infections, respectively, anti-interleukin-23 was present.
“The study of Cheng et al provides support that anti-interleukin-23 autoantibodies contribute to adult-onset immunodeficiency,” Mihai G. Netea, M.D., Ph.D., and Frank L. van de Veerdonk, M.D., Ph.D., from the Radboud University Medical Center in Nijmegen, Netherlands, write in an accompanying editorial. “At the clinical level, this study should lead to the design of new diagnostic tests and therapeutic approaches based on anti-interleukin-23 autoantibodies in patients with rare and severe infections of unknown cause.”
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