B Cell-Activating Factor (BAFF) in Inflammatory Bowel Disease: BAFFling No Longer?

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.

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Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa048 ◽

2020 ◽

Vol 14 (9) ◽

pp. 1222-1230 ◽

Cited By ~ 1

Author(s):

T Severyns ◽

J Kirchgesner ◽

J Lambert ◽

C Thieblemont ◽

A Amiot ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

B Cell ◽

Bowel Disease ◽

Cohort Analysis ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

B Cell Lymphomas ◽

Free Survival ◽

Significant Difference ◽

Inflammatory Bowel

Abstract Background and Aims The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. Methods A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. Results A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. Conclusions In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

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P078 Proteomics and Lipidomics Analysis Revealed Alterations of Complement Activation and Lipid Metabolism in peripheral blood mononuclear cells of Inflammatory Bowel Disease Patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.207 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S180-S181

Author(s):

S Notararigo ◽

S Bravo ◽

M Martin-Pastor ◽

I Baston-Rey ◽

A Quiroga-Castiñeira ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Lipid Metabolism ◽

B Cell ◽

Bowel Disease ◽

Cell Activation ◽

Mononuclear Cells ◽

Serum Samples ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Inflammatory Bowel

Abstract Background The lack of interaction between immune system cells and microbiota is considered a key driver of the pathogenesis of inflammatory bowel disease (IBD). The association of age-associated B cells (ABC) from antigen-experienced B cells and autoimmunity is now well established. The increased demands in lipid metabolism during immune response and cell activation upon autoimmune signals leads to lipid tag modifications of proteins. In IBD patients, we observed an impairment of B cell development, identifying a transitional B cell subset expressing CD38Hi, CD24Hi and CD19+. We hypothesize that metabolic alterations of proteins and lipids during immune cell activation might be a relevant mechanism of autoimmune disease. Methods An IBD cohort of patients in clinical remission under anti-TNF treatment was included in order to test metabolic and proteomic changes in peripheral blood mononuclear cells (PBMCs). Proteomic analysis was performed by Mass Spectrometry using a label free quantitative method (SWATH-MS analysis) and lead to identify a number of proteins underregulated (< 0.6) and overexpressed (> 1.5) fold change respect to control. Lipidomics of serum samples analyzed by proton Nuclear Magnetic Resonance spectroscopy (NMR)2 and multivariant statistics. Results Serum samples were obtained in Crohn disease (CD) n = 18, ulcerative colitis (UC) n = 9, before biological infusion and healthy controls (CTRL) n = 10. Proteins related with lipid metabolism like APOC2 for CD and APOB, APOA1 for UC, were differentially modulated. Significant differences in non-polar metabolites and lipids that phenotypically define CD and UC groups respect to CTRL were observed (Fig. 1) Fig. 1 Orthogonal-Partial Least Square-Discriminant Analysis (OPLS-DA) of the global NMR data of the serum samples of groups CD and CTRL. Indeed, proteins associated with complement activation like Complement Factor 1 and Complement C1q subcomponent subunit B were differentially expressed in CD group. These results were confirmed by lipidomic analysis, in which palmitic (Fig. 2) as well as other candidate lipids were more abundant in IBD groups than CTRL. Fig 2. Differences of palmitic acid concentration in CD and UC patients vs CTRL (Bonferroni test showed statistical difference between CTRL vs. CD and CTRL vs. UC with p = 0.02 and p = 0.004 respectively). Conclusion Our study detected high levels of proteins regulating lipid metabolism and palmitic in IBD patients. This observation can be interpreted as part of deleterious alterations of proteins through palmitoylation during B-cell activation and might be a relevant mechanism of disease. Further exploration of palmitate catabolism might shed light to the mechanisms that result in immunometabolic disorders.

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TLR2 and TLR4 regulate B cell responses in human inflammatory bowel disease

Inflammatory Bowel Diseases ◽

10.1097/00054725-200812001-00025 ◽

2008 ◽

Vol 14 ◽

pp. S8 ◽

Cited By ~ 1

Author(s):

A Noronha ◽

Y Liang ◽

W Harnett ◽

M Harnett ◽

A Stucchi ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

B Cell ◽

Bowel Disease ◽

Cell Responses ◽

Human Inflammatory Bowel Disease ◽

Inflammatory Bowel ◽

B Cell Responses

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Epstein–Barr virus replication linked to B cell proliferation in inflamed areas of colonic mucosa of patients with inflammatory bowel disease

Journal of Clinical Virology ◽

10.1016/j.jcv.2010.09.011 ◽

2011 ◽

Vol 50 (1) ◽

pp. 31-36 ◽

Cited By ~ 21

Author(s):

Sumathi Sankaran-Walters ◽

Kanat Ransibrahmanakul ◽

Irina Grishina ◽

Jason Hung ◽

Enrique Martinez ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Cell Proliferation ◽

B Cell ◽

Virus Replication ◽

Bowel Disease ◽

Epstein Barr Virus ◽

Colonic Mucosa ◽

Barr Virus ◽

Inflammatory Bowel ◽

Epstein Barr

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The Role of T Follicular Helper Cells and Interleukin-21 in the Pathogenesis of Inflammatory Bowel Disease

Gastroenterology Research and Practice ◽

10.1155/2021/9621738 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Lulu Sun ◽

Ruixue Kong ◽

Hua Li ◽

Dashan Wang

Keyword(s):

Inflammatory Bowel Disease ◽

B Cell ◽

Antibody Production ◽

Bowel Disease ◽

B Cell Lymphoma ◽

Tfh Cells ◽

Follicular Helper ◽

Inflammatory Bowel ◽

Interleukin 21

T follicular helper (Tfh) cells represent a novel subset of CD4+ T cells which can provide critical help for germinal center (GC) formation and antibody production. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), inducible costimulatory molecule (ICOS), B cell lymphoma 6 (BCL-6), and the secretion of interleukin-21 (IL-21). Given the important role of Tfh cells in B cell activation and high-affinity antibody production, Tfh cells are involved in the pathogenesis of many human diseases. Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases characterized by symptoms such as diarrhea, abdominal pain, and weight loss. Ulcerative colitis (UC) and Crohn’s disease (CD) are the most studied types of IBD. Dysregulated mucosal immune response plays an important role in the pathogenesis of IBD. In recent years, many studies have identified the critical role of Tfh cells and IL-21 in the pathogenic process IBD. In this paper, we will discuss the role of Tfh cells and IL-21 in IBD pathogenesis.

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