IL-23/IL-17A Dysfunction Phenotypes Inform Possible Clinical Effects from Anti-IL-17A Therapies

Biologics that neutralize specific cytokines have improved outcomes for several immune-mediated disorders but may also increase risks for particular side effects. This article postulates potential immuno-logic consequences of inhibiting components of the IL-23/T-helper cell 17 pathway–the target of next-generation biologics for treating psoriasis–based on clinical phenotypes of inherent or acquired deficien-cies in this pathway. Generally, downstream deficien-cies (e.g., IL-17A, IL-17F) are associated with fewer disorders compared with upstream deficiencies, sug-gesting that selectively blocking downstream targets may result in a narrower range of side effects. However, safety of these specific inhibitions must be established in long-term studies