bluuebunny/crossref_metadata_2025 huggingface dataset:
P009 Integrin-b7+ cytotoxic MAIT cells are expanded in the colon of Ulcerative Colitis patients, correlate with disease severity and are targeted by vedolizumab therapy
Authors: Hermangild Kottoor S , Ibraheim H , Polychronis P , Senthuran B , Jameson E , Samaan M , Irving P , Powell N
Published: January 2022

Background

Mucosal-associated invariant T (MAIT) cells are major histocompatibility complex (MHC) class Ib-restricted innate-like lymphocytes with anti-bacterial functions that are enriched at mucosal sites. Their role in ulcerative colitis (UC) is unknown.

Methods

Colonic biopsies and peripheral blood were collected from patients with active UC (n=34) and healthy control subjects (n=14). Peripheral blood mononuclear cells (PBMC) and Lamina propria mononuclear cells (LPMC) were isolated and activated in vitro with PMA/ionomycin followed by surface and intracellular staining and multiparametric flow cytometry analysis. T cell populations, including gamma delta T cells (TCR gamma delta+), iNKT cells (TCR Vα24-Jα18+), MAIT cells (TCR Vα7.2+ CD161+), CD4, CD8 T cells and their intracellular expression of IL17A, TNF, IFN-g, IL22, IL13 and granzyme B (GZMB) were determined. MAIT cells were further characterised as CD8+, CD4+, CD8 CD4 double positive (DP), CD8 CD4 double negative (DN) cells and expression of the gut homing integrin-b7.

Results

DN cells were the most common MAIT subset in the colon and were significantly increased in both UC patients and HC subjects compared to peripheral blood. In UC, DN MAIT cells exhibited a cytotoxic phenotype, with significantly higher production of Granzyme B (median 45.0% of cells) compared to DN MAIT cells in HC (median 17%, P<0.005). DN MAIT cells in UC gut also co-produced significantly higher proportion of IL17A (median 22% in UC vs 7% in HC, P<0.006) and TNF (median 61% in UC vs 10% in HC, P<0.02) compared to DN MAIT cells from HC. In UC patients, the proportional abundance of cytotoxic DN MAIT cells accumulating in the colon significantly correlated with disease activity (UCEIS) score (r2=0.34, P<0.0007).

The number of DN MAIT cells expressing integrin-b7 was also significantly higher in UC patients compared to HC (median 66% in UC vs 32% in HC, p<0.001). In UC patients initiated on vedolizumab therapy, the proportional abundance of cytotoxic, DN MAIT cells accumulating in the colon significantly fell at week 14 in comparison with their pre-treatment abundance (median 25% vs 51%, P<0.001). Following vedolizumab induction, the reduction in the abundance of colonic cytotoxic DN MAIT cells correlated with endoscopic improvement (r2=0.45, p=0.0085).

Conclusion

DN MAIT cells with cytolytic activity and augmented expression of multiple cytokines are enriched in the colon of UC patients in numbers that correlate with the magnitude of mucosal injury. Vedolizumab treatment reduces DN MAIT cell accumulation in the colon and the magnitude of reduction correlates with treatment response.
P011 New insights into the pathogenic potential and signalling network of NKG2D+ CD4+ T-cells in Crohn’s Disease
Authors: Modos D , Gul L , Lo J , Madgwick M , Cozzetto D , Lord G , Korcsmaros T , Powell N
Published: January 2022

Background

A subset of mucosal CD4+ T-cells expressing the NK cell receptor NKG2D (encoded by the KLRK1 gene) are enriched in patients with Crohn’s Disease (CD). In pre-clinical models of colitis, NKG2D expression was confined to a subset of colonic CD4+ T-cells that hyper-expressed interferon gamma. However, the functional role of these cells in mediating intestinal inflammation is unknown. Little is known about the transcriptional regulation of this population or the key signalling networks that they engage.

Methods

Pre-clinical models of CD, adoptive transfer experiments and in vitro culture systems were used to investigate the phenotype and pathogenicity of NKG2D using Klrk1-/- and WT mice. Signalling networks and interactions between NKG2D, key transcription factors and relevant cytokines were investigated by probing published single-cell RNA seq data (Martin et al. Cell 2019). Pathway members of potential interactions were collected from the literature, and the OmniPath database and we applied a heat propagation model.

Results

NKG2D-expressing T-cells were potently pathogenic when adoptively transferred to Rag1- mice, mediating more severe disease than Klrk1-/- CD4+ T-cells. Notably, Klrk-/- T-cells were still able to induce colitis, indicating that NKG2D-independent pathogenic pathways also exist.

Chromatin immunoprecipitation demonstrated that T-bet bound at the transcriptional start site of the Klrk1 locus in WT Th1 cells, but not Tbx21-/- Th1 T-cells. There were significantly fewer NKG2D expressing CD4+ T-cells from Tbx21-/- mice, and forced expression of T-bet in Tbx21-/-Ifng-/- double knockout CD4+ T-cells induced Klrk1 mRNA expression, consistent with T-bet being a transcriptional activator of the Klrk1 gene.

The NKG2D model network reached FOS, NFKB and JUN transcription factors depending on the presence of the NKG2D. The model distinguished two comparable pathway activation - one with active PRKCA in T-cells including CD8+ T-cells and one with less active PRKCA mostly in macrophages. Comparing the inflamed and uninflamed conditions, highly activated T-cells, and a population of Th17+ TRM cells had an active KLRK pathway only in inflamed Crohn disease.

Conclusion

NKG2D expressing colonic CD4+ T-cells are potent cytokine producing cells and are more colitigenic than their NKG2D-negative counterparts. Network-based heat propagation showed that specific populations of colonic memory T cells are active only in the inflamed condition, meanwhile, the model identified two types of cells that had active KLRK1 pathway: one which was PRKCA dependent activity and one which had non-PRKCA dependent activity. We also identify T-bet as an important transcriptional regulator of NKG2D expression.
P039 The role of α4β7+CLA+ ‘dual tropic’ T cells in inflammatory bowel disease
Authors: Gordon H , Rodger B , Hornsby E , McGuire J , Kok K B , Lindsay J O , Stagg A J
Published: January 2022

Background

Upon activation, T cells upregulate cell-surface molecules that enable entry into peripheral tissues. Retinoic acid (RA) produced by gut DC induces integrin α4β7 required for gut homing and represses CLA which facilitates skin entry; hence, these markers are usually reciprocally expressed. We aimed to identify the mechanisms enabling dual tropism, define the properties of α4β7+CLA+ T cells and compare blood and intestinal α4β7+CLA+ T cells in health and IBD.

Methods

Using flow cytometry, expression of α4β7 and CLA was assessed on (i) ex vivo human T cells from blood and intestinal tissue and; (ii) naïve CD4 T cells stimulated in vitro with antibodies (anti-CD3/28/2), or allogeneic DCs. The role of RA signalling and p38MAPK in CLA expression were investigated with respective antagonists Ro41-5253 and SB203580. Transwell studies were used to investigate whether DC-T cell direct contact was required for CLA expression. Single cell RNA sequencing (scRNAseq) of in vitro activated T cells was undertaken, with feature barcode antibody labelling of β7 and CLA. Differential gene expression and pathway analysis was undertaken.

Results

DC-activated T cells contained both α4β7+ and CLA+ cells and included a dual tropic population co-expressing both markers. In contrast, antibody-activated T cells expressed α4β7 but did not express CLA unless RA receptor alpha (RARa) signalling was also inhibited. The DC-derived signals that allowed CLA expression were partially dependent on p38MAPK and required DC-T cell contact for optimal activity. A high frequency of dual tropic T cells produced IFNg or TNFa.

ScRNAseq identified 270 genes differentially expressed (fold change <-2 or >+2, FDR<0.01) between α4β7+CLA+ and α4β7+CLA- T populations generated by DC stimulation. Expression of FUT7, a fucosyltransferase implicated in generation of the CLA moiety, was increased in the α4β7+CLA+ population and overall 27 pathways were significantly enriched (p<0.05) in this population, including intestinal immune networks and IBD.

Ex vivo, CD4+ and CD8+ dual tropic T cells were found in peripheral blood and intestinal tissue. CD4+ dual tropic T cells were significantly increased in the colon of patients with IBD (p=0.03).

Conclusion

DC-derived signals acting via p38MAPK generate pro-inflammatory dual tropic T cells even in the presence of active RA signalling. CLA expression may act as an additional ligand in gut trafficking by binding to selectins on the inflamed vascular endothelium and has a potential role in both gut and skin inflammation in IBD.
P041 Characterization of cytokine and drug concentrations in serum, mucosa and faeces during induction treatment of moderate-to-severe ulcerative colitis with anti-TNF monoclonal antibodies
Authors: Van Oostrom J , Hanzel J , Verstockt B , Singh S , Smith J , Stylli J , Vermeire S , D’Haens G
Published: January 2022

Background

It remains unclear why up to 30% of patients with moderate-to-severe ulcerative colitis (UC) do not respond to anti-TNF treatment (anti-TNF). In this study, we explored multi compartment cytokine and anti-TNF concentrations in peripheral blood (PB), faeces (F) and colonic mucosa (CM) before, during and after anti-TNF induction treatment in UC.

Methods

91 UC patients starting infliximab or adalimumab were included at two tertiary centres (table 1). Patients underwent clinical and endoscopic assessment with CM, PB, and F sampling at baseline. Follow-up CM samples were taken at first follow-up endoscopy during the first year. Follow-up PB and F samples were taken at follow-up endoscopy and optionally on day 3, 7, 14, and 28.

Response (R) was defined as Mayo endoscopic score (MES) 0–1 (assessed by a blinded independent reader) and subsequent anti-TNF therapy for > 1 year. All other patients were classified as non-responders (NR).

TNFα, IL6, IL10 and drug levels were measured in all compartments and OSM and IL12p40 in PB and CM (F anti-TNF with ELISA and cytokines and PB and CM anti-TNF with a bead-based immunoassay). CM samples were normalised for gram of protein (gop).

To differentiate pharmacokinetic (PK) from pharmacodynamic (PD) failures, we calculated CM anti-TNF/ TNFα. We classified values above the median as sufficient PK (Good PK) and values below as insufficient PK (Bad PK).

Results

We analysed CM, PB and F samples from 71, 91 and 32 patients respectively. Baseline cytokine concentrations were similar in all compartments.

At follow-up (table 2), PB IL6 was lower in R (p=0.045). All F cytokines were significantly higher in R (TNFα: p<0.001; IL6: p<0.001; IL10: p<0.001). In CM, IL6 and OSM were lower and IL12p40 higher in R (IL6: p=0.004; OSM: p=0.01; IL12p40: p=0.021).

After stratification of CM samples for PK readouts (table 3, figure 1), IL6 was highest in Good PK NR vs Good PK R (6905 vs 2980 ng/gop, p = 0.002) and OSM was lowest in R vs NR groups (2466 vs 36111 ng/gop in Good PK R vs Good PK NR, p = 0.002). Trends were observed towards highest IL10 in Bad PK R and Highest IL12p40 in Good PK R, although not significant.

Conclusion

Baseline cytokine concentrations in PB, CM and F did not predict response to anti-TNF induction treatment in UC. At follow-up, response (R) was characterised by lower PB IL6; higher F cytokines; lower CM IL6 and OSM and higher IL12p40.

After stratification for PK, pharmacodynamic failure (Good PK NR) was characterised by highest CM IL6, indicating it is a driver to inflammation alternative to anti-TNF. R was characterised by lowest OSM regardless of PK, indicating OSM mainly reflects disease activity. Further research focuses on cytokine-PK interplay contributing to anti-TNF (non-) response.
P067 Human intestinal CD103+SIRPα+ conventional dendritic cells from patients with Crohn′s disease prime IL-17+ T-cells
Authors: Bernardo D , Arribas-Rodriguez E , De Castro C G , Fiz-Lopez A , De Prado A , Fernandez-Salazar L , Barrio J , Izquierdo S , Garcia-Alonso J , De Andres B , Garcia-Abril J M , Romero A , Sanchez-Gonzalez J , Garrote J A , Arranz E
Published: January 2022

Background

Crohn’s disease (CD) is a chronic inflammation of the human gastrointestinal tract. Intestinal conventional dendritic cells (cDC) maintain the balance between immunity against pathogens and tolerance towards nutrients and commensals. However, there is not much information about DC composition, phenotype and function in the human gut in CD.

Methods

Human intestinal resections were obtained from patients with ileocolonic CD and proximal colonic cancer. Both inflamed and non-inflamed tissue was obtained from the ileum and colon from CD patients. The non-affected tissue from the proximal (terminal ileum) and distal (proximal colon) sides of the colonic cancer resections (minimum 10cm distance from the tumor) constituted the reference tissue.

Tissue was disaggregated and cDC and macrophages enriched by flow-sorting. Human intestinal cDC were identified within singlet viable leukocytes as CD14-CD64-HLA-DR+CD11c+. Type 1 cDC (cDC1) were defined as CD103+SIRPα- while type 2 cDC (cDC2) and identified as SIRPα+ and further divided into subsets based on the expression of CD103. Macrophages were identified within singlet viable leukocytes as CD14+CD64+HLA-DR+. All three cDC subsets and total macrophages were used to stimulate allogeneic CD4+ naïve T-cells which were further characterized by flow cytometry.

Results

All 3 human intestinal cDC subsets from non-CD controls were able to stimulate naïve T-cells as opposed to intestinal macrophages. Indeed, stimulated T-cells produced IL-10 and co-expressed FoxP3, being this capacity increased in both CD103+ subsets (CD103+SIRPα- and CD103+SIRPα+). Moreover, all three ileal cDC subsets stimulated T-cells more efficiently than their paired colonic counterparts, although the acquired T-cell profile did not differ among tissues. None of the cDC subets, on the contrary, induced the expression of IFNγ or IL-17 on stimulated T-cells. Referred to CD patients, all three colonic cDC subsets were more stimulatory than their counterparts from the control tissue, while CD103+SIRPα+ cDC from the inflamed ileum primed the generation of IL-17+ responding T-cells.

Conclusion

All human intestinal cDC subsets prime the generation of regulatory FoxP3+ and IL-10+ T-cells. This capacity was increased in both CD103+SIRPα- and CD103+SIRPα+, in agreement with the regulatory functions attributed to CD103+ cDC. All ileal cDC subsets were also more stimulatory than their colonic counterparts. Nevertheless, colonic cDC from CD patients were more stimulatory that non-CD controls, rendering CD103+SIRPα+ cDC from the inflamed tissue in CD with a higher capacity to generate Th17 cells, which suggests that their regulatory functions can be reshaped by the inflamed tissue microenvironment.
P069 Design and delivery of anti-oxidant inorganic complexes mimicking the superoxide dismutase for inflammatory bowel diseases treatment
Authors: Schanne G , Zoumpoulaki M , Demignot S , Delsuc N , Policar C , Seksik P
Published: January 2022

Background

Oxidative stress (OS), defined by an increased flux of reactive oxygen species (ROS), plays an important role in the pathogenesis, the perpetuation and the amplification of inflammatory bowel diseases. In normal state, enzymatic defenses regulate the concentration of ROS but in IBD, some of them, including the superoxide dismutase (SOD), are weakened. The use of molecules mimicking the SOD activity may compensate for this deficiency and reduce the OS. 4 molecules were characterized for their SOD activity, their stability and their inertness. Their anti-inflammatory activity were assessed in a cellular model of epithelial inflammation and in a murine model of colitis and correlated to their physico-chemical properties.

Methods

The studied SOD mimics display similar structures differing by the presence of a propyl and a cyclohexyle group aiming to improve their kinetic inertness. To generate an inflammation associated to ROS production, intestinal epithelial (HT29) cells were stably transfected to over-express MD2, a co-receptor for LPS binding to TLR-4 receptor. The cells were stimulated by LPS (0.1µg/mL) and incubated with the SOD mimics (6 hours, 0,1-100µM). The secretion of IL-8 was measured by ELISA and the MnSOD expression by Western Blot. The SOD mimics were administrated to a murine model of colitis chemically-induced by DNBS. To protect them from the gastric acidity, the mimics were encapsulated in delivery vector. The monitoring of weight and the determination of intestinal permeability and macroscopic scores were performed.

Results

The mimics containing a cyclohexyle group display kinetic rates for metal exchanges that are up to 30-fold lower meaning that they are more inert. At 100µM, the four SOD mimics induced a significative decrease in IL-8 secretion (<35%/positive control (PT), p<0,02) and in MnSOD expression (<20%/PT, p<0,033). At 10µM, only the mimics containing the cyclohexyle group are still able to significatively counteract the LPS-induced secretion in IL-8 (<30/PT, p<0,001) and over-expression of MnSOD (20%/PT, p<0,02). Their bioactivity at lower doses can be correlated to their higher inertness. Concerning in vivo activity, preliminary assays show a faster recovery of the mice, that have received the SOD mimics with the cyclohexyle group. 3 days following DNBS injection, the mice of this group recovered in average 89% of their starting weight while the control mice recovered only 83%.

Conclusion

The SOD mimics display anti-inflammatory and antioxidant activity on HT29-MD2 cells, which is dependent on their inertness. Assays on a murine model of colitis seems to follow the same trend. The use of antioxidant treatments based on SOD mimics may reduce the inflammation rising from oxidative stress in IBD.
P116 Screening for low BMI and unintentional weight loss alone is insufficient to identify patients at risk for malnutrition in an outpatient IBD population
Authors: Hendrix E M B , Spooren C E G M , Grommen D , Mujagic Z , Pierik M J , Jonkers D M A E
Published: January 2022

Background

Inflammatory bowel disease (IBD) is associated with malnutrition, which can further impair disease course and quality of life. Therefore, guidelines advocate screening of patients in clinical practice. The prevalence of malnutrition in IBD-cohorts however, varies widely, mainly due to differences in parameters used. The primary aim of the present study was to assess the prevalence of malnutrition using single and a combined set of parameters (Global Leadership Initiative on Malnutrition (GLIM) criteria). Secondary aims were i) to evaluate the accuracy of screening recommendations given in current IBD guidelines and ii) to explore which patients have an increased risk of malnutrition.

Methods

Malnutrition was defined by the GLIM criteria, based on the combination of a phenotypic (i.e. non-volitional weight loss, low body mass index (BMI), or reduced muscle mass) and an etiologic criterium (i.e. reduced food intake or assimilation, and disease burden or inflammation). Malnutrition was also determined using single parameters for impaired body composition, muscle strength or caloric intake (Table 1), and the combination of low BMI and unintentional weight loss as advised in current IBD guidelines. To screen for malnutrition, the Short Nutritional Assessment Questionnaire (SNAQ) and Malnutrition Universal Screening Tool (MUST) were completed. Independent risk factors (i.e. clinical and demographic factors) for malnutrition were analyzed by multivariable logistic regression.

Results

Of the 200 included patients (139 CD, 61 UC), 41 (20.5%) fulfilled the GLIM criteria, 95 (47.5%) had at least one parameter for malnutrition impaired (Figure 1). The fat free mass index was most often affected. When unintentional weight loss and/or low BMI was used as screening marker for nutritional status in line with current IBD guidelines, 29 (14.5%) patients would have been identified (Figure 2). Screening for malnutrition using the SNAQ and MUST detected 44 (22.0%) and 23 (12.9%) patients with a positive score. Only female sex was associated with malnutrition when at least one parameter was impaired (OR 2.47, 95% CI 1.35–4.51).

Conclusion

Malnutrition prevalence among IBD outpatients according to the GLIM criteria was found to be 20.5%. Almost half of the IBD outpatients had malnutrition as defined by various single parameters and irrespective of disease characteristics. Screening instruments and/or markers according to current IBD guidelines, did not identify a substantial part of the patients. Therefore, screening for malnutrition is recommended for all IBD outpatients by multiple parameters, with special attention for assessing fat free mass and reduced intake.
P125 Ankylosing spondylitis can influence the outcome of inflammatory bowel disease
Authors: Jun Y K , Kim A H , Park J , Choi E , Yoon H , Kang H W , Lee H J , Im J P , Kim J S , Seong-Joon K
Published: January 2022

Background

Both inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) are inflammatory diseases but there was little previous study that demonstrate the IBD severity and outcome in IBD patients with concomitant AS.

Methods

Patients’ records were collected from 3 tertiary hospitals (Seoul national university hospital, Seoul national university Bundang hospital, and Seoul metropolitan government Seoul national university Boramae medical center) from October 2004 to June 2021. Patients with IBD and concomitant AS (IBD-AS group) were identified and propensity score matching (PSM) was applied to match the IBD-AS group and IBD patients without AS (only IBD group).

Results

After PSM, significantly more patients in IBD-AS group had colectomies (p = .017) or were prescribed biologics (p < .001), immunosuppressive agents (p = .021), and steroid (p = .017) than in only IBD group. The number of patients treated with biologics (p < .001) or immunosuppressive agents (p = .032) were significantly greater in UC-AS group than in only UC group. There was no significant difference in outcomes between only CD group and CD-AS group. In logistic regression analyses, identified that concomitant AS was a significant factor associated with biologics treatment in patients with IBD. Kaplan-Meier analyses demonstrated that there was a significant difference in the probability of starting biologics treatment between IBD patients with and without concomitant AS (p = 0.002). In UC patients, the probability of starting biologics was also significantly different according to concomitance of AS (p < 0.001). Concomitant AS was a risk factor for predicting biologics treatment in patients with UC in Cox regression analysis after adjustment UC (adjusted hazard ratio, 6.296; confidence interval, 2.243 to 17.668; p < 0.001)

Conclusion

Patients with IBD-AS group were more likely to have a higher severity than in only IBD group. The current study result can help IBD specialists understand and treat patients with IBD and concomitant AS better.
P133 Point-of-care measurement of infliximab and adalimumab trough levels by the fluorescence resonance energy transfer (FRET) assay
Authors: Cerna K , Kastylova K , Sebek P , Luxova S , Lukas M
Published: January 2022

Background

Therapeutic drug monitoring (TDM) is the clinical practice of measuring serum drug concentrations to guide clinical decision-making. In IBD patients, it is applied mainly in infliximab (IFX) and adalimumab (ADL) therapy. TDM is either performed reactively in response to disease activity, or proactively in the absence of symptoms. The aim of the present study was to compare two analytical methods for the detection of trough infliximab and adalimumab levels (TL): point-of-care (POCT) fluorescence resonance energy transfer (FRET) method, and the enzyme- linked immunosorbent immunoassay (ELISA).

Methods

TL IFX were measured in n=24 and TL ADL in n= 21 blood samples. For ELISA, standard peripheral venous samples were used, and for POCT FRET measurements, capillary finger puncture was performed. Two assay results were compared evaluating the regression relationship using Spearman’s correlation coefficient and the Bland-Altman plots. Cohen’s kappa analysis was used to compare the degree of qualitative agreement between the two data sets. Repeatability was assessed by the difference of the repeated measurements, their means and standard deviations.

Results

The high degree of correlation was found between the measured values, both qualitative and quantitative (p < 0.0001 for both IFX and ADL), either expressed by the Spearman’s correlations, or by Bland-Altman analysis. Cohen’s weighted kappa 0.903 for IFX and 0.834 for ADL showed substantial/almost perfect agreement of qualitative results. Closeness of the agreement of successive measurements was very acceptable for both TLs of both drugs.

Conclusion

Point-of-care detection of IFX and ADL trough levels by FRET is accurate, comparable to the reference method, analysis is sufficiently consistent. For clinical sites with a proactive approach to TDM, FRET may be a useful tool for decision-making regarding individualization of biologic therapy.

Acknowledgements: We thank ProciseDX company for the ProciseDX analyzer rental, and for providing the laboratory diagnostics.
P135 Usefulness of clinical and ultrasound indices to assess enthesis lesions in patients with inflammatory bowel diseases
Authors: Gainullina G , Abdulganieva D , Kirillova E , Odintsova A
Published: January 2022

Background

The aim of the study was to assess existing clinical and ultrasound indices for the evaluation of enthesopathies in patients with inflammatory bowel diseases (IBD).

Methods

95 pts with IBD were prospectively enrolled into the study: 55 of them with ulcerative colitis (UC) and 40 with Crohn’s disease (CD). Clinically we counted tender entheses in 46 points of the upper and lower extremities. LEI (Leeds Enthestis Index) (0–6 points), MASES (Maastricht Ankylosing Spondylitis Enthesitis Score) (0–13 points) and the SPARCC index (Spondylarthritis Research Consortium of Canada) (0–16 points) were calculated. Ultrasound examination was performed in B-mode and PD-mode. Entheseal hypoechogenicity, entheseal thickening, presence of vascularization were considered as acute lesions. Bone erosions and enthesophytes were considered as chronic lesions. GUESS (Glasgow Ultrasound Enthesitis Scoring System) (0–36 points), MASEI (Madrid Sonography Enthesitis Index) (0–136 points) and BUSES (Belgrade Ultrasound Enthesitis Score) (0–132 points) were calculated. Spearman coefficient used to calculate correlations.

Results

In pts with tender ≥ 1 enthesis, the LEI was positive in 26% of patients, the MASES index - in 7%, the SPARCC index - in 18%, the US indices were positive in a larger number of patients: GUESS - in 47%, MASEI - in 40% and BUSES - 54%.A total of 6460 entheses were examined using Doppler ultrasound. The number of enthesites was 293/6460 (4.5%), the number of enthesites with vascularization was 62/6460 (1.0%), the number of erosions was 313/6460 (4.8%), the number of enthesophytes was 91/6460 (1, 4%).A direct correlation is observed between the number of enthesites and LEI indices (SR = 0.54; p = 0.00), MASES (SR = 0.42; p = 0.00), SPARCC (SR = 0.54; p = 0, 00), GUESS (SR = 0.22; p = 0.02), BUSES (SR = 0.32; p = 0.001), as well as between the number of enthesitis with vascularization and LEI indices (SR = 0.24; p = 0.017), MASES (SR = 0.34; p = 0.00), GUESS (SR = 0.23; p = 0.022), MASEI (SR = 0.32; p = 0.001), BUSES (SR = 0, 29; p = 0.003). A statistically significant relationship was found between the number of erosion and the GUESS indices (SR = 0.48; p = 0.00), MASEI (SR = 0.49; p = 0.00), BUSES (SR = 0.5; p = 0, 00), as well as between the number of enthesophytes and the GUESS indices (SR = 0.75; p = 0.00), MASEI (SR = 0.28; p = 0.00), BUSES (SR = 0.57; p = 0.00).

Conclusion

Acute lesion of enthesis in patients with IBD can be assessed using both clinical (LEI, MASES, SPARCC) and ultrasound indices (GUESS, MASEI, BUSES). To assess chronic lesions (erosion, enthesophyte) changes in enthesis in patients with IBD, it is preferable to use ultrasound indices.
P159 Faecal S100A12 as a non-invasive marker of inflammatory activity in Inflammatory Bowel Disease
Authors: Cenni S , Casertano M , Caprio A M , Pacella D , Miele E , Martinelli M , Staiano A , Strisciuglio C
Published: January 2022

Background

Calgranulin-C (f-S100A12) and zonulin are considered faecal marker of intestinal inflammation. The aim of our study was to evaluate f-S100A12 and fecal zonulin as alternative markers in the follow-up of IBD children to monitore the disease activity and to predict the clinical and endoscopic relapse, compared with FC and serum inflammatory markers.

Methods

Between September 2019 and March 2020, we prospectively enrolled all IBD pediatric patients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC). S100A12, zonulin and faecal calprotectin (FC) were determined by enzyme-linked immunosorbent assay (ELISA).

Results

One hundred seventeen consecutive children, 39.3% with CD and 71 60.7% with UC were enrolled. No differences were found for FC, f-S100A12 and zonulin values in UC and CD. In both CD and UC there was a direct correlation between FC and f- S100A12 levels (r=0.54; p<0.001 and r = 0.63; p<0.001, respectively). F-S100 correlated directly with fibrinogen (r=0.32; p=0.038), platelets count (r=0.35; p=0.021), WBC (r=0.39; p=0.009) and SES CD (r=0.459, p=0.004) and inversely with hemoglobin (r= -0.40; p=0.0077), hematocrit (r=-0.43; p=0.015). In patient with UC we found a direct correlation between f-S100 and CRP (r=0.252; p=0.040) and platelet count (r=0.254; p=0.038). There was no correlation between f-S100A12 and PUCAI or PCDAI score. No association was found between Paris and fecal biomarkers evaluated both in CD and UC. No significant correlation were found between zonulin and the different parameters studied.

Conclusion

Our data suggest that f-S100A12 and FC but not F-zonulin are useful non-invasive biomarkers in the management of pediatric IBD in follow up and to monitor endoscopic relapse in CD patients.
P180 The prevalence and clinical course of atypical distribution of inflammation in newly diagnosed ulcerative colitis
Authors: Kim N Y , Lee Y J , Kim K O , Kim E S , Lee H S , Kim S K , Jang B I , Kim E Y , Cho K B , Kim J
Published: January 2022

Background

Ulcerative colitis (UC) is characterized by continuous mucosal inflammation extending from rectum to the proximal lesion. However, there are cases of atypical distribution of inflammation, such as appendiceal orifice inflammation (AOI), skipped lesion, and rectal sparing. This study aimed to evaluate the prevalence and clinical course of atypical distribution of inflammation in newly diagnosed UC.

Methods

Between 2013 and 2021, 374 patients who underwent a colonoscopy at the time of diagnosis of UC were retrospectively reviewed. Clinical courses including relapse rate within 1-year, 2-year of diagnosis and exposure to immunomodulator or biologics during follow-up were retracted from the prospective IBD registry (ClinicalTrial.gov, NCT02193464). Atypical UC was defined as patients with AOI, skipped lesion or rectal sparing at initial colonoscopy. The clinical courses and changes of endoscopic findings were compared between typical UC group and atypical UC group.

Results

Of 374 patients, 116 (31.0%) categorized as atypical UC; specifically, 90 (24.1%) showed AOI, 17 (4.5%) showed rectal sparing and 49 (13.1%) showed skipped lesion. When 90 patients with AOI were reclassified according to the extent of inflammation, 62(16.6%) had a localized inflammation at peri-appendiceal area, 13(3.5%) had an inflammation of the entire cecum, 15(4.0%) had an inflammation extends to the proximal A-colon. The clinical courses of atypical UC were not different from typical UC group, however, patients with skipped lesion showed a lower 1-year relapse rate compared to those without skipped lesion (P=0.042). Of 96 patients with atypical UC who underwent follow-up endoscopy, 73 (75.8%) demonstrated a typical distribution of UC at their follow-up colonoscopy.

Conclusion

Atypical distribution of UC including AOI, skipped lesion, and rectal sparing are not uncommon in patient with newly diagnosed UC. However, most of these features do not appear to correlate significantly with prognosis in the clinical course of UC. In majority of patients with atypical UC, the lesion turned into typical UC on follow-up colonoscopy.
P183 A systematic review on outcome measures of long-term efficacy in clinical trials concerning Crohn’s disease patients
Authors: Janssen L , Creemers R , van Bodegraven A , Pierik M
Published: January 2022

Background

Treatment goals for Crohn’s disease (CD) tend to shift from clinical towards endoscopic remission as a potential means to reduce intestinal damage. Additionally, sustained corticosteroid (CS) free remission is warranted to prevent drug related side effects.

In clinical trials, long-term efficacy of treatment is assessed by a range of outcome measures at variable time points. Besides clinical activity, it is recommended by the EMA to measure biochemical and endoscopic activity, given the poor correlation between commonly applied clinical activity indices and mucosal inflammation. Finally, STRIDE advices to add a PROM given the frequent perception gap in disease control between patient and health care professionals.

Moreover, the relapsing-remitting nature of CD challenges timing of efficacy evaluations. Use of cross-sectional outcomes only on predetermined moments disregards the health status in between these measurements.

In this systematic review, we provide an overview of the outcomes employed to assess long-term efficacy of maintenance (drug) therapy or treatment strategies in randomized controlled trials and their open label extensions in CD patients.

Methods

A systematic search of Pubmed and Embase databases was performed. Giving the emerging treatment goals, the search was restricted to trials published since 2007.

Two independent reviewers screened titles and abstracts and selected eligible trials. We assessed whether and when long-term (i.e. >48 weeks) clinical, biochemical and/or endoscopic efficacy outcomes were used. In addition, data on patient perspective and CS use were collected.

Results

Sixty-seven out of 1947 articles were included (figure 1).

Clinical activity indices were used in 66 studies (99%) as long-term efficacy outcome, with 20 studies (30%) taking into account concomitant CS use. C-reactive protein concentration was (part of) an outcome in 29 studies (43%), and faecal calprotectin in 15 studies (22%). Endoscopic activity was evaluated in 30 studies (45%). PROMs were used in 29 studies (43%), with IBDQ being the most frequently used. Seven studies measure long-term clinical, biochemical, endoscopic activity and patient perspective, in three studies a sustained CS free status as part of the outcome was required (table 1). In most studies cross-sectional measures or multiple measurements over time, so-called panel data, were used.

Conclusion

We established a lack of objective outcome measures of inflammation and patient perspective in clinical trials in CD, consequently missing pivotal data to evaluate current treatment goals. Additionally, cross-sectional outcomes on fixed time points were mostly applied, resulting in loss of efficacy information in chronic relapsing-remitting diseases.
P186 Can transabdominal bowel ultrasound accurately detect both small and large bowel Crohn Disease in pediatric patients when compared to MRE?
Authors: Hudson A , Huynh H Q , Ma H , Kuc A , Kim J , Almeida P , Carroll M W , Wine E , Thompson A , Isaac D M
Published: January 2022

Background

Magnetic resonance enterography (MRE) has been the modality of choice to assess small bowel inflammation in patients with Crohn disease (CD). It can also assess large bowel when not feasible to assess endoscopically. Transabdominal bowel ultrasound (TABUS) is an attractive non-invasive tool to assess CD activity. Studies to date have focused on its correlation to large bowel endoscopic findings in adult CD. This study aimed to compare TABUS and MRE in identifying small and large bowel CD in pediatric patients.

Methods

Pediatric patients (≤18 years old) seen for suspected CD were prospectively enrolled and underwent baseline TABUS, endoscopy, MRE, blood work and stool studies. The Pediatric Crohn’s Disease Activity Index (PCDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) were used to assess disease activity. Bowel wall thickness (BWT) was assessed by TABUS and MRE. TABUS measurements were scored with the Simple Ultrasound Activity Score for Crohn Disease (SUS-CD) (0=≤3mm, 1=3–4.9mm, 2=5–7.9mm, 3=≥8mm). Pearson Chi-square was used to compare BWT between TABUS and MRE.

Results

21 patients (71% male) were included, with a median age of 13 years (range 6–16). Median PCDAI was 40 (25–49) and SES-CD 15 (6.5–22). There was a high level of agreement between MRE and TABUS (Figure 1) with some disagreement in the jejunum (n=9/21, 43%). For terminal ileal (TI) disease where there was disagreement, endoscopy of TI was in agreement with TABUS in two patients and MRE in five patients. Endoscopic TI disease that was documented as normal on TABUS was mild (SES-CD 3). In patients with abnormal MRE, BWT was not significantly different between the two modalities (Table 1). In patients with normal MRE, TABUS SUS-CD scores were accurately 0 in almost all segments (score 1 in TI) (Table 2). TABUS correctly identified no fistulae and 2 small bowel strictures (identified at endoscopy), but did not detect 1 intra-abdominal abscess and 4 large bowel strictures (only 1 stricture seen on endoscopy). Excessive lymph nodes (>4) were successfully seen on TABUS in 10/16 patients. TABUS correctly identified 75% of patients with significant mesenteric fibrofatty proliferation. Hyperemia on TABUS corresponded to an abnormal MRE for that segment in 92–100% of small bowel and 50–86% of large bowel.

Conclusion

TABUS and MRE are comparable modalities in the assessment of small and large bowel disease in newly diagnosed pediatric CD patients. Assessment of proximal small bowel is complex, and MRE may over-call disease. MRE still plays an important role in assessing abscesses and mild large bowel narrowing. Hyperemia on TABUS is an important indicator of active bowel inflammation, and is particularly useful for endoscopically inaccessible small bowel.
P193 Correlation of the IBD Disk scores with diagnosis of IBD, Faecal calprotectin and Endoscopic scores in patients presenting to a rapid access IBD inception clinic
Authors: Shariff S , Sharma N , Quraishi M N , Cooney R , Iqbal T , Rimmer P
Published: January 2022

Background

The IBD-Disk was adapted from the Inflammatory Bowel Disease –Disability Index as a tool to capture a patient’s functional status for Health Care Professionals to review. Patients complete this disk for ten symptoms with scores ranging from 0 to 10. Patients with higher scores have a significant burden of disease. We explore correlation of IBD disk score with faecal calprotectin, endoscopic scores, and a diagnosis of IBD in patients referred to our inception clinic service.

Methods

Patients with symptoms compatible with Inflammatory Bowel Disease (IBD) and a raised faecal calprotectin are fast tracked to our rapid access inception clinic service for further assessment. We prospectively collected data on demographics, faecal calprotectin levels and IBD disk scores. We assessed correlation between the total score and individual components of the IBD disk score with demographics, faecal calprotectin (F.Cal) at presentation and subsequent diagnosis of IBD and endoscopic scores. Descriptive and multivariate regression analysis was performed.

Results

68 patients (47% female; median age 35.5 years [IQR 16.8]) attending the inception clinic were included in this analysis. Of these patients 17/68 (25%) were diagnosed with Crohn’s disease (CD), 18/68 (26%) with ulcerative colitis (UC) and 5/68 (7%) with indeterminate colitis. 33 (33.8%) had unclear diagnoses and are currently undergoing further investigation. IBD was excluded in 5/68 (7%) patients. Younger patients (age 15 – 30 years) and patients above 60 years of age had a relatively higher F.Cal at presentation (Figure 1).

The total IBD disk score was significantly higher in younger patients (p=0.03). No correlation was seen between the eventual diagnosis of IBD and total score at presentation or individual components of the IBD disk score. Multivariate regression analysis, however, demonstrated significant correlation between regulated defecation and interpersonal interactions with F.Cal at baseline in patients with IBD (p<0.05). No correlation was seen with other variables of the IBD disk and faecal calprotectin levels.

IBD Disk score as well as Harvey Bradshaw index correlated well with Simple Endoscopic Score in Crohn’s disease (SES-CD) (Figure 2). No significant correlation was seen between IBD Disk score and baseline F.Cal or Endoscopic Mayo Score. The simple Mayo score showed a better correlation between F.Cal and Endoscopic Mayo score than IBD Disk.

Conclusion

Correlation of F.Cal with certain elements of the IBD Disk tool highlights its utility in capturing both inflammatory and non-inflammatory related disability in patients with IBD. IBD Disk Scores correlate with CD endoscopic severity scores (ie SES-CD) but not UC scores (ie Endoscopic Mayo Score).
P194 A modified Rutgeerts score of i2a after ileocolic resection for Crohn’s Disease: endoscopic recurrence or anastomotic healing?
Authors: Van Der Does De Willebois E , Duijvestein M , Wasmann K , D’Haens G , Buskens C , Bemelman W
Published: January 2022

Background

The reliability and reproducibility of scoring endoscopic recurrence is of utmost importance because it generally determines initiating postoperative medical therapy and it is used as outcome parameter in clinical trials. Variability in endoscopic scoring may result in inappropriate therapeutic decisions and study conclusions. It is hypothesised that different types of anastomoses have an influence on scoring endoscopic recurrence using the Rutgeerts’ score. The aim of this study is to analyse to what extent the ulcerations are determined by the type of anastomosis and how it interferes with the scoring of Crohn’s recurrence.

Methods

This is a retrospective review of endoscopy videos to re-assess endoscopic recurrence. All videotapes of the ileocolonoscopy were blinded and scored by a trained gastroenterologist (MD) and a surgeon (WB). Videos were excluded if the quality of the video was low or if the anastomosis was not visualised properly. The primary outcome is the presence of ulcerations six months after surgery, on individual parts of the anastomosis: inverting stapled anastomosis (side to side conjunction) and everting type of junction (transection ends). In the latter group, at least one site – colon, ileum or both – was scored.

Results

Of 99 available endoscopy videos, eighty-nine eligible patients were included in this retrospective study for analysis. The inverting and everting stapled anastomosis were scored individually using the SES-CD. A SES-CD of zero was found in 21/89 (23.6%) of the inverting anastomoses versus 74/75 (98.67%) in the everting anastomoses.

Conclusion

This study demonstrated a significant difference in wound healing of the inverting anastomosis versus the everting anastomosis. Inverting anastomoses show ulcerations and a circular scar long after surgery irrespective of the presence of ulcerations of terminal ileum. A normal wound healing phenomena might mistakenly be seen for recurrent Crohns’ disease. Everting anastomosis, on the contrary, heal without residue.
P209 Disproportionate low albumin and high neutrophil-to-lymphocyte ratio in small bowel adenocarcinoma in long-term Crohn’s disease patients
Authors: Veisman I , Oppenheim A , Sub laban Z , Kenig A , Ukashi O , Shacham-Shmueli E , Engel T , Kopylov U , Ben-Horin S , Lang A
Published: January 2022

Background

Although Crohn’s disease (CD) is a known risk factor for small bowel adenocarcinoma (SBA), early diagnosis remains a significant clinical challenge with many cases diagnosed inadvertently during small bowel resection or biopsies performed for presumed active or structuring CD. Identification of biomarkers for SBA may lead to early detection and improved prognosis in CD patients. The aim of the study was to explore a possible association between two simple laboratory values – serum albumin levels and neutrophil-to-lymphocyte ratio (NLR) and SBA in CD patients.

Methods

A retrospective case-control study comparing long-standing (>10 years) CD patients who have undergone small bowel (SB) resection with carcinoma detection by histopathology examination, compared with long-standing CD patients who underwent SB resection without malignancy detection at a ratio of 1:3 of cases to controls. Demographics, disease behavior, NLR, albumin levels and total parenteral nutrition (TPN) status during the three months period prior to surgery were retrieved and compared between groups.

Results

Forty-two patients with long-standing CD were included (11 with SBA and 31 patients without SBA). Median age was 55 [Interquartile range (IQR) 44–65] in the malignancy group and 37 (IQR 31–47) in the no-malignancy group (p-value < 0.05). Median NLR in the three months prior to surgery was 8.5 (IQR 6.2–31.3) in SBA patients and 3.8 (IQR 2.8–5.3) for patients without SBA (p < 0.05). Mean albumin levels during the three months period prior to surgery were significantly lower among patients with SBA compared with patients without SBA (2.6 ± 0.6 g/dL versus 3.5 ± 0.6 g/dL, respectively, p < 0.05), despite SBA patients being treated with TPN for significantly longer duration.

Conclusion

CD patients with SBA have statistically significant increased NLR and lower albumin compared with surgically treated CD patients without SBA. If corroborated by further studies, high NLR and disproportionate low albumin levels in long-duration CD patients may be useful biomarkers of SBA.