New and Evolving Immunotherapy in Inflammatory Bowel Disease

Raad, Mohamad A.; Chams, Nour; Sharara, Ala I.

doi:10.1159/000445986

Cited by 19 publications

(17 citation statements)

References 79 publications

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“…This finding could be of clinical utility in defining treatment goals and end-point parameters in the context of personalized medicine. Furthermore, it supports previously published data on the sphingolipid metabolism as a therapeutic target in IBD 53,54 .…”

Section: -Discussionsupporting

confidence: 90%

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State

Diab

Hansen

Goll

et al. 2019

Inflammatory Bowel Diseases

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Background The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects. Methods Treatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified. Results The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups. Conclusion This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state.

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Section: -Discussionsupporting

confidence: 90%

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State

Diab

Hansen

Goll

et al. 2019

Inflammatory Bowel Diseases

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“…As a consequence there is no causative treatment available and administrated therapeutic strategies continue to depend mostly on systemic immunosuppression being just one link in the complicated chain of interactions. Introduction of biologic therapy directed against tumor necrosis factor (TNF)- α over two decades ago improved clinical outcomes in IBD patients and paved the way for other immunotherapies [ 3 ]; still the effectiveness of IBD treatment does not exceed 50% [ 4 ]. With new therapeutic modalities being tested and implemented to the clinical practice, noninvasive biomarkers, which may assist in the diagnosing and monitoring of IBD as well as in predicting the disease course and treatment effectiveness, are needed [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral Lymphocytes of Patients with Inflammatory Bowel Disease Have Altered Concentrations of Key Apoptosis Players: Preliminary Results

Neubauer

Woźniak−Stolarska

Krzystek−Korpacka

2018

BioMed Research International

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Notwithstanding uncertain pathogenesis of inflammatory bowel disease (IBD), deregulation of adaptive immunity is paramount for the development of inflammation. Essential role in the resolution of inflammation is played by apoptosis, deregulated in lymphocytes isolated from inflamed intestine. Despite IBD being a systemic disease, little is known about apoptosis of peripheral lymphocytes. The concentrations of Bcl-2, cytochrome c, p53, and caspase-9 were determined (ELISA) in lymphocyte-enriched fractions of peripheral blood mononuclear cells (LE-PBMCs) from 64 individuals (42 with IBD) and related to IBD phenotype and activity, treatment, and inflammatory and hematological indices. The diagnostic potential of evaluated markers was determined as well. All evaluated molecules were significantly lower in IBD patients, of which cytochrome c and p53 were significantly lower exclusively in patients with Crohn's disease (CD) and cytochrome c differed significantly between CD and ulcerative colitis (UC). Caspase 9 was significantly lower in active IBD and Bcl-2 in active UC whereas cytochrome c was higher in active CD. Treatment with corticosteroids affected the concentrations of cytochrome c and p53. Both positively correlated with hsCRP and the concentrations of all markers were interrelated. As IBD markers, Bcl-2 and caspase-9 displayed good accuracy and, as a panel of markers with cytochrome c, their accuracy was excellent (92%). As CD markers Bcl-2, cytochrome c, and p53 displayed fair accuracy but combined determination of Bcl-2 and cytochrome c improved the accuracy to 85%. Taken together, our results imply diminished intrinsic apoptotic capacity of LE-PBMCs in IBD but an upregulation of proapoptotic features parallel to increasing severity of inflammation. Observed abnormalities in intrinsic pathway of apoptosis are more pronounced in CD. Upon positive validation on a larger set of patients, combined quantification of Bcl-2 and cytochrome c might be considered as an adjunct in differential diagnosis of UC and CD of colon and rectum.

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“…Although rs11209026 G/A SNP may have functional and phenotypic consequences on ACS, the molecular basis of the genetic variation is remains unclear. The SNP rs11209026 G/A, located in exon 9 of the IL-23R, has been associated with strong protection against Crohn's disease (allele A), which means that allele A is underrepresented in the disease population [15] [16]. We and others have recently observed protective nature of rs11209026 allele A.…”

Section: Discussionmentioning

confidence: 87%

Relationship between IL-23R rs11209026 Gene Polymorphism and Susceptibility to Acute Coronary Syndrome

Wang¹,

Li²,

Song³

et al. 2018

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Background: Several studies illustrated that IL-23/Th17 axis could be an important pro-inflammatory pathway in atherosclerosis. As a key element in this inflammatory mechanism, interleukin-23 receptor (IL-23R) may play a critical role in the pathological process of atherosclerosis. Single nucleotide polymorphisms (SNPs) in IL-23R have recently been consistently found to be associated with atherosclerosis diseases. However, its association with acute coronary syndrome (ACS) is still indistinct. Here, we discussed whether genetic polymorphisms in IL-23R (rs11209026 G/A) were associated with susceptibility to ACS. Methods: Among 160 patients with ACS, it includes 80 patients with unstable angina pectoris (UAP), 80 patients with myocardial infarction (MI), and 80 control subjects were selected randomly. The polymorphisms of IL-23R (rs11209026 G/A) were analyzed by the Sanger method. Results: Data showed that percentages of rs11209026 AG genotypes were significantly lower in ACS group (including: UAP and MI) than in controls (odds ratio [OR] = 0.324, 95% confidence interval [CI]: 0.148-0.712, p = 0.005; OR = 0.351, 95% CI: 0.135-0.910, p = 0.031; OR = 0.303, 95% CI: 0.112-0.817, p = 0.018, respectively). Furthermore, there was no correlation between rs11209026 G/A SNP and dyslipidemia-associated ACS. Conclusions: The variant of the rs11209026 polymorphism in IL-23R gene might decrease the risk of ACS, and these data suggest that AG genotype of the rs11209026 G/A polymorphism may act as a protective factor for acute coronary syndrome and subtype of ACS.

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New and Evolving Immunotherapy in Inflammatory Bowel Disease

Cited by 19 publications

References 79 publications

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State

Peripheral Lymphocytes of Patients with Inflammatory Bowel Disease Have Altered Concentrations of Key Apoptosis Players: Preliminary Results

Relationship between IL-23R rs11209026 Gene Polymorphism and Susceptibility to Acute Coronary Syndrome

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