Intestinal homeostasis alteration toward mucosal inflammation with blocking IL-17 in psoriasis patients: a case...

Interleukin (IL)-17 is a key cytokine in various inflammatory disease. Targeting IL-17 signals blockage did not improve inflammatory bowel disease (IBD) clinically, but also even developed de novo enteritis in non-IBD subjects. Little is known about the effects of blocking IL-17 signaling on intestinal homeostasis. This study investigated intestinal immunity under the inhibition of IL-17 signaling.

Refractory patients with psoriasis who started receiving anti-IL-17 or anti-IL-17 receptor inhibitors were included in this case series. These patients never experienced IBDs. Evaluation for fecal immunochemistry test (FIT), fecal calprotectin (fCal), endoscopic findings, colonic mucosa histology, and fecal microbial composition before and 3 months after starting treatment on the subjects was performed. Fecal microbial composition was analyzed with 16S rRNA. We present a series of 5 cases. The median age was 64 years, the disease duration was 31 years, two were female, four received secukinumab, and one received brodalumab. The median FIT level and fCal level was 0 ng/mL [interquartile range (IQR), 19.5 ng/mL] and 39.4 mg/kg (IQR, 304 mg/kg) at baseline. Thereafter, the median FIT level and fCal level on 3 months after initiating antibody therapy increased to 19 ng/mL (IQR, 15 ng/mL) and 222 mg/kg (IQR, 71 mg/kg), respectively. Endoscopic findings before administration showed mild edema in one patient and mild redness in one patient, and thereafter these two patients showed unchanged endoscopic findings, and one patient showed new mild edema and another patient showed new mild redness after administration. The number of mononuclear cells infiltrating in the mucosa significantly increased with antibody administration. Microbial community analysis did not show alteration in alpha diversity after antibody administration. Proteobacteria was increased after the administration.

Although no one occurred clinical symptoms after IL-17 inhibition in this case series, blocking IL-17 signals altered intestinal homeostasis toward mucosal inflammation.