Peptide/Antibody–Drug Conjugates for Therapeutic Applications in Inflammatory Disease

Future Therapeutic Approaches for Inflammatory Bowel Diseases

Rac1 Takes Center Stage in Pancreatic Cancer and Ulcerative Colitis: Quantity Matters

A Genomewide Analysis Provides Evidence for Novel Linkages in Inflammatory Bowel Disease in a Large European Cohort

Winter Is Coming! Clinical, Immunologic, and Practical Considerations for Vaccinating Patients With Inflammatory Bowel Disease During the Coronavirus Disease-2019 Pandemic

Inflammatory Bowel Disease Extending Its Reach

Bidirectional relationship between atopic dermatitis and inflammatory bowel disease: A systematic review and meta-analysis

This Month in Gastroenterology

AGA Medical Position Statement on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease

Background Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive. Methods In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD and other inflammatory diseases were analysed using multiplexed immunohistochemistry . Other inflammatory diseases comprised five patients with intestinal tuberculosis, and five with intestinal Behçet’s disease. Additionally, a separate prospectively maintained "vedolizumab (VDZ) cohort", established in 12 ulcerative colitis(UC) patients who underwent endoscopic biopsy before VDZ administration was analysed to predict response to VDZ. Results In the immunohistochemistry analysis, the cell density of T cell subsets, including helper T cell (Th), cytotoxic T cell (Tc), regulatory T cell (Treg), PD-1+ cell, PD-1+ Th, PD-1+ Tc, and PD-1+ Treg was investigated and compared between IBD and other inflammatory disease. Cell densities of PD-1+ cells (p=0.028), PD-1+ Th (p=0.008), and PD-1+ Treg (p=0.024) were higher in IBD compared with other inflammatory disease.(Figure 1) In addition, the proportion of PD-1+ cells in Th and Treg was higher in the IBD group than in the other inflammatory disease group (median 7% vs. 3%, p=0.008; median 6% vs. 2%, p=0.004, respectively). Comparing within IBD, the cell density of Treg was higher in Crohn’s disease(CD) than in UC (p=0.042), whilst the cell density of Tc was higher in CD than in UC with marginal statistical significance (p=0.066). In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1+ cells (p=0.026), PD-1+ Th (p=0.026), and PD-1+ Treg (p=0.041) than the no response group.(Table 1) Conclusion We explored the relationship between PD-1 expression and IBD using multiplexed immunohistochemistry. We compared IBD and other inflammatory disease in their expression of various immune cells including PD-1+ cells, and found IBD had higher PD-1 expression, as well as higher PD-1+ Th and PD-1+ Treg compared with other inflammatory diseases. In addition, VDZ-responsive patients had higher PD-1 expression. Our study confirmed the difference in PD-1 expression in IBD and other inflammatory diseases and revealed that PD-1 expression could be a predictive marker for VDZ responsiveness.

The anatomic pathology of inflammatory bowel disease (IBD) is necessarily studied and continually evaluated for better understanding of its scope and meaningful classification. The reasoning behind classification is to enable grouping of ailments for reliable treatment and prognostication. The two prominent IBD are traditionally subclassified as ulcerative colitis (UC) and Crohn's disease (CD). They are separated from most other IBD by two features: (1) their idiopathic nature and (2) their chronicity. Superb descriptions of their anatomic manifestations abound in literature and their salient features can be found in selected articles and specialty texts [1-12]. Despite the apparent redundancy, some of this chapter will be devoted to the traditional descriptions. During much of the past century many inflammatory diseases of the alimentary tract have been subclassified and to a considerable degree great insight into pathogenesis has been gained [13-18]. This is particularly true for infectious gastroenterocolitides, food intolerance, and to some extent iatrogenic injury (such as radiation or drug effects). What remains are a number of idiopathic inflammatory diseases, the dominant ones being UC and CD. It is the responsibility of our generation and future ones to continue the progression and place our new understanding of IBD in the context of modern understanding of biology and medicine. With this in mind, even the traditional practice of gross examination and microscopic study can contribute to 21st-century understanding of IBD. The anatomic pathologic findings in IBD can be separated into those estabUshed traditional findings, and those that are more modern based on relatively recent descriptions. Interestingly, some of the modern anatomic pathological interpretations may have their root in our modern treatment and diagnostic techniques which are unmasking previously under-recognized elements of IBD. Of particular interest in this chapter are more recent anatomic descriptions regarding (1) patchy rather than diffuse changes in UC, (2) upper gastrointestinal CD, and (3) epithelial neoplasia in IBD. The general aspects of the anatomic pathology of UC and CD are reviewed here, and the histopathologic assessment is covered in detail in Chapter 37. Classification of disease is always a challenge in medicine, and IBD are no different. For this chapter the strategy for classification separates inflammatory diseases with a known etiology from idiopathic IBD. It also nearly excludes diseases in which the bowel is secondarily involved by systemic diseases (such as Behcet syndrome). However, even within IBD one can subclassify the diseases based on fulminant course, extent of colitis, and indeterminate clinicopathologic disease. Thus, it is important to preserve some large diagnostic groups for the purpose of rapid understanding and communication, and for this reason we stress separating IBD into the two major groups: UC and CD. Smaller concerns addressing ulcerative proctitis or indeterminate colitis are less strongly treated. There are ample anatomic pathologic features to separate UC and CD, but also some unifying principles. Fortunately, a good foundation of pathologic principles helps to understand the medically relevant aspects of IBD. All of IBD has, at its pathophysiologic root, chronic inflammation with activity. Long-standing inflammation has the ability to injure the bystander organ, often beyond the ability for repair and normal function. Like any chronic inflammatory process, the longterm consequences are parenchymal damage, atrophy, fibrosis, and loss of function to the injured anatomic compartment. Like so many other chronic inflammatory processes in the gastrointestinal (GI) tract there is an increased risk of malignancy. Thus, the pathophysiologic sequelae of UC and CD are in parallel with other organs of the GI system which suffer chronic inflammatory injury; the examples

Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients With Inflammatory Bowel Disease

Inflammatory bowel disease is characterized by clinical remission and relapse caused by severe intestinal inflammation. Drug therapy for inflammatory bowel disease is associated with unpleasant side effects. Furthermore, efficacy of conventional drugs decreases with chronic use, which can be a major difficulty in the long-term management of this disease. In active inflammatory bowel disease, leukocytes are elevated with activation behavior and increased survival time, and mucosal neutrophil level parallels the severity of intestinal inflammation and predicts relapse. Leukocyte-derived inflammatory cytokines are suspected to be major factors in the initiation and perpetuation of inflammatory bowel disease. Accordingly, leukocytes should be appropriate targets for therapy. To reduce peripheral blood level of leukocytes, centrifugation has been used to deplete peripheral blood leukocytes; this provided the initial evidence that reducing the level of peripheral blood leukocytes can benefit patients with inflammatory disease. To overcome the limitations of centrifugation, membrane filters, such as the Cellsorba trade mark column and leukocyte-adsorbing beads containing column like Adacolumn, have been developed that are direct blood perfusion systems for removing any desired level of leukocytes. In initial independent clinical studies, these two new models have produced striking clinical efficacy, safety, and a marked reduction in the dose of corticosteroids used to induce remission of active inflammatory bowel disease. Leukocytapheresis has been associated with a significant decrease in the amount of several proinflammatory cytokines produced by peripheral blood leukocytes. Accordingly, the Japan Ministry of Health has now approved both methods for the treatment of active ulcerative colitis. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy for inflammatory bowel disease to promote remission, taper conventional drug dosage, and potentially reduce the number of patients who require colectomy. The results should further understanding of the pathophysiology of inflammatory bowel disease.

Introduction. Axial spondylitis is a chronic inflammatory disease primarily affecting the axial skeleton but can also involve peripheral joints. Axial spondylitis is often associated with extra-articular manifestations, such as inflammatory bowel diseases, emphasizing the need for rigorous monitoring and personalized therapeutic approaches. The interactions between axial spondylitis and inflammatory bowel diseases fall under the concept of “immune-mediated inflammatory diseases”, sharing common pathogenetic mechanisms. This study analyzes the prevalence and characteristics of inflammatory bowel diseases in patients with axial spondylitis. Objective. The objective of this study was to describe the baseline characteristics of patients with axial spondylitis, evaluate the prevalence of inflammatory bowel diseases in this population, and identify correlations between the two conditions, contributing to a better understanding of their pathogenetic and clinical interactions. Material and methods. This prospective observational study included 257 axial spondylitis patients followed over two years. Patients were selected according to ASAS criteria for axial spondylitis and clinical guidelines for inflammatory bowel diseases. Analyses included clinical evaluations, laboratory tests, and imaging studies. Data were processed using SPSS v22.0. Continuous variables were expressed as mean ± standard deviation or median and interquartile range, and categorical variables as percentages. Correlations were assessed using Spearman’s coefficient, with results considered significant at p<0.05. Results. Among the 257 patients included (168 men and 89 women, mean age 48.2 ± 13.1 years), 13.2% were recently diagnosed with axial spondylitis. Of these, 5.1% had inflammatory bowel diseases, distributed as follows: Crohn’s disease (3.1%), ulcerative colitis (1.2%), and indeterminate colitis (0.8%). In 53.8% of cases, the diagnosis of inflammatory bowel diseases preceded axial spondylitis. Multivariate analysis identified the absence of a family history of axial spondylitis as a significant risk factor for inflammatory bowel diseases (OR = 3.4; p = 0.025). The prevalence of inflammatory bowel diseases increased with axial spondylitis duration, reaching 6.5% in patients with disease progression over eight years. Conclusions. The study highlights a high prevalence of inflammatory bowel diseases in axial spondylitis patients, indicating the need for rigorous clinical monitoring. The absence of a family history of axial spondylitis was identified as a major risk factor for inflammatory bowel diseases. These findings emphasize the importance of a multidisciplinary clinical approach, including active screening for inflammatory bowel diseases and collaboration between rheumatologists and gastroenterologists, to improve patient prognosis and quality of life.

Characterization of Myeloid Neoplasms in Inflammatory Bowel Disease

Endoplasmic reticulum (ER) stress is a causative factor of inflammatory bowel diseases. ER stress mediators, including CCAAT enhancer-binding protein (C/EBP) homologous protein (CHOP), are elevated in intestinal epithelia from patients with inflammatory bowel diseases. The present study arose from the question of how chemical ER stress and CHOP protein were associated with nuclear factor-κB (NF-κB)-mediated epithelial inflammatory response. In a human intestinal epithelial cell culture model, chemical ER stresses induced proinflammatory cytokine interleukin-8 (IL-8) expression and the nuclear translocation of CHOP protein. CHOP was positively involved in ER-activated IL-8 production and was negatively associated with expression of peroxisome proliferator-activated receptor γ (PPARγ). ER stress-induced IL-8 production was enhanced by NF-κB activation that was negatively regulated by PPARγ. Mechanistically, ER stress-induced CHOP suppressed PPARγ transcription by sequestering C/EBPβ and limiting availability of C/EBPβ binding to the PPARγ promoter. Due to the CHOP-mediated regulation of PPARγ action, ER stress can enhance proinflammatory NF-κB activation and maintain an increased level of IL-8 production in human intestinal epithelial cells. In contrast, PPARγ was a counteracting regulator of gut inflammatory response through attenuation of NF-κB activation. The collective results support the view that balances between CHOP and PPARγ are crucial for epithelial homeostasis, and disruption of these balances in mucosal ER stress can etiologically affect the progress of human inflammatory bowel diseases.