English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

To the Editor: IL10 is an immunoregulatory cytokine that has a central role in the maintenance of intestinal mucosal homeostasis and prevention of colitis [1]. Loss-of-function mutations in IL10, IL10RA, or IL10RB cause severe intestinal inflammation and perianal disease that presents in the first months of life and is refractory to conventional immunosuppressive medications such as steroids, anti-TNFα antibodies, and immunomodulators [2]. The definitive treatment for IL10R deficiency is an allogeneic hematopoietic stem cell transplantation (HSCT) to reconstitute IL10 signaling, if a suitable donor is available. Unfortunately, the clinical condition of many of these patients is not amenable to transplant at the time of their diagnosis. As such, a therapeutic bridge is needed to prepare them for transplant. We have recently shown that IL1β is highly upregulated in IL10R deficiency [3], and blocking IL1 attenuated colitis in an IL10R-deficient mouse model. Thus, we elected to treat two patients with medical-refractory severe inflammatory bowel disease (IBD) secondary to IL10R deficiency with anakinra, an IL1 receptor antagonist. In both cases, high dose anakinra therapy (10–12 mg/kg/day) led to marked clinical, endoscopic, and histological improvement within a few weeks [3]. To date, this is the first report of treatment that suppressed the hyperactive immune response in the gut of these patients. Herein, we present additional information on one of these patients, a 28-year-old IL10R-deficient patient with a history of severe infantile-onset IBD, whose condition improved significantly after anakinra treatment. This patient initially presented with bloody diarrhea and was diagnosed with IBD at 6 months of age. He underwent a subtotal colectomy with end ileostomy at age 7 years and developed enterocutaneous fistulae at the age of 18. At age 23, a large B cell lymphoma was discovered and he received R-CHOP chemotherapy. An ileoscopy at age 28 demonstrated severe ileitis (Fig. 1a) and examination of the abdominal wall revealed multiple enterocutaneous fistulae. After the confirmation of an IL10RA loss-of-function mutation in this patient, he was started on anakinra. During the initial 2 weeks of treatment dose escalated to 12 mg/kg/day subcutaneously. At 4 weeks, a repeat ileoscopy showed he had a substantial improvement in his mucosal inflammation (Fig. 1a). The patient also experienced a significant decrease in his ileostomy output and marked weight gain within a few months. There were no significant changes in his serum inflammatory markers. Overall, The original version of this article was revised: The article title was mistakenly amended to “Increased Mucosal IL-22 Production of an IL-10RA Mutation Patient Following Anakin Treatment Suggests Further Mechanism for Mucosal Healing”.

Increased Mucosal IL-22 Production of an IL-10RA Mutation Patient Following Anakinra Treatment Suggests Further Mechanism for Mucosal Healing