Immunological Effects of Anti.IL-17/12/23 Therapy in Patients with Psoriasis Complicated by Candida Infections

Biologics that block the T helper (Th) 17 pathway are very effective in the treatment of psoriasis and other inflammatory diseases. However, IL-17 is also crucial for antifungal host defense, and clinical trial data suggest an increase in the incidence of Candida infections during IL-17 inhibitor (IL-17i) therapy. We investigated the innate and adaptive immune responses of patients with psoriasis with a history of skin and/or mucosal candidiasis during IL-17i or IL-12/23 inhibitor therapy, comparing those responses with those of healthy controls. Patients with psoriasis with IL-17i showed significantly lower CD4thornTh1-like (CCR6(-)CXCR3(+) CCR4(-)) and Th1 Th17-like (CD4(+) CCR6(+) CXCR3(+) CCR4(-)) cell percentages. Patient cells stimulated with Candida albicans produced significantly lower IL-6 in the IL-12/23 inhibitor group and IL-1 beta in the IL-17i group, whereas the release of TNF-alpha and ROS was similar between patients and controls. IFN-gamma and IL-10 production in response to several stimuli after 7 days was particularly decreased in patients receiving IL-17i therapy. Finally, after stimulation with the polarizing cytokines IL-1 beta and IL-23, the Th17 cytokine response was significantly lower in the IL-17i patient group. These innate and adaptive immune response defects can diminish antifungal host immune response and thereby increase susceptibility to candidiasis in patients treated with IL-17i or IL-12/23 inhibitor.

Automated summary

Biologics that block the Th17 pathway are effective in treating inflammatory diseases like psoriasis but may increase the risk of Candida infections. This study found that patients with psoriasis receiving IL-17 inhibitors had impaired immune responses, leading to reduced antifungal defense and increased susceptibility to candidiasis.