Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn’s Disease and Ulcerative Colitis

Abstract Objectives The objective of this study was to assess current treatment patterns of pediatric ulcerative colitis (UC) and Crohn’s disease (CD) patients, using data in the ImproveCareNow (ICN) registry. Methods Pediatric (2–17 years) patients in the United States who were newly diagnosed with UC or CD between June 1, 2013-December 31, 2019, who had their first recorded ICN visit within 6 months of diagnosis and who were actively followed for at least 12 months (± 90 days) were included in this study. Descriptive statistics of baseline patient demographics were summarized for the overall IBD patient population and separately for UC and CD. Treatment patterns (including use of corticosteroids, 5-aminosalicylic acid (5-ASA), 6-mercaptopurine/azathioprine (6-MP/AZA), methotrexate, tumor necrosis factor inhibitors (TNFi) [adalimumab, infliximab, certolizumab, golimumab, and their biosimilars], ustekinumab, vedolizumab, and other medications [natalizumab and tofacitinib]) were assessed at the initial baseline visit, and at 1-year and 3-year time points. Results A total of 6,504 pediatric IBD patients (UC=1,784; CD=4,720) were included in this study. Patients had a mean age at diagnosis of 13.0 years (UC=13.2; CD=12.9), 57.1% were male (UC=49.6%; CD=60.0%), and 81.0% were White (UC=81.2%; CD=81.0%) (Table 1). At the initial ICN visit, 46.4% of UC patients were prescribed a corticosteroid, while 19.8% received a 5-ASA, 12.6% received a TNFi, 10.4% received a 6-MP/AZA, 3.0% received methotrexate, and 0.3% received vedolizumab. At the initial visit, 40.2% of CD patients were prescribed a corticosteroid, while 29.1% received a TNFi, 18.5% received a 6-MP/AZA, 12.4% received methotrexate, and 3.3% received a 5-ASA. At the 1-year and 3-year time points, rates of 5-ASA and corticosteroid use decreased among UC patients; however, rates of 6-MP/AZA, methotrexate, and TNFi increased (Table 2). Similarly, at the 1-year and 3-year time points, rates of corticosteroids among CD patients decreased; however, rates of methotrexate and TNFi increased (Table 2). There was also an increase in use of ustekinumab and vedolizumab over time among UC and CD patients. Conclusion These results highlight the current treatment patterns of pediatric UC and CD patients in the United States. At the initial ICN visit, the 46% of UC and 40% of CD patients were receiving corticosteroids, however, at 1-year and 3-years after initial visit, over 30% of UC patients and over 60% of CD patients were receiving TNF inhibitors with considerably reduced corticosteroid use.

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The First Year—Crohn's Disease and Ulcerative Colitis: An Essential Guide for the Newly Diagnosed

Gastroenterology ◽

10.1053/gast.2002.1230953 ◽

2002 ◽

Vol 123 (3) ◽

pp. 953

Author(s):

Anthea L. Darling

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

First Year ◽

Newly Diagnosed

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STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn’s Disease

Journal of Immunology Research ◽

10.1155/2019/9406146 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ying Tang ◽

Sanda A. Tan ◽

Atif Iqbal ◽

Jian Li ◽

Sarah C. Glover

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Immune Responses ◽

Tyrosine Phosphorylation ◽

Innate Lymphoid Cells ◽

Immune Defense ◽

Lymphoid Cells ◽

Dependent Manner ◽

Regulatory Pathways ◽

Innate Effector

Crohn’s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele “A” with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 “A” risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse.

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