title: IL-23/IL-17A Dysfunction Phenotypes Inform Possible Clinical Effects from Anti-IL-17A Therapies.
abstract: 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 immunologic 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 deficiencies in this pathway. Generally, downstream deficiencies (e.g., IL-17A, IL-17F) are associated with fewer disorders compared with upstream deficiencies, suggesting 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.
authors.affiliation: Department of Dermatology, Oregon Medical Research Center, Portland, Oregon, USA. Electronic address: ablauvelt@oregonmedicalresearch.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Blauvelt
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lebwohl
authors.affiliation: Department of Dermatology, Innovaderm Research, Montreal, Quebec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Bissonnette
mesh_terms: D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D053759:Interleukin-23 / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy / Q000503:physiopathology; D010641:Phenotype; D011565:Psoriasis / Q000188:drug therapy / Q000503:physiopathology; D012480:Salmonella Infections / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D001688:Biological Products; D020381:Interleukin-17; D053759:Interleukin-23