FC Levels Research Articles

Clinical Severity of Visceral Leishmaniasis Is Associated with Changes in Immunoglobulin G Fc N-Glycosylation

ABSTRACT Visceral leishmaniasis (VL) has a high fatality rate if not treated; nevertheless, the majority of human infections with the causative agent, Leishmania infantum chagasi, are asymptomatic. Although VL patients often present with increased levels of serum immunoglobulins, the contribution of antibodies to resistance or progression to disease remains unknown. Effector and regulatory functions of antibodies rely on their interactions with type I and II Fc receptors, and these interactions are tuned by the patterns of antibody Fc N-glycosylation. In view of these facts, we applied a robust method of IgG Fc N-glycopeptide profiling of serum samples from 187 patients with VL, 177 asymptomatic individuals, 116 endemic controls (individuals residing in areas where VL is endemic) and 43 nonendemic controls (individuals living in an area where VL is not endemic). We show that, in comparison to the overall IgG Fc N-glycan profiles of asymptomatic or uninfected healthy individuals, those of patients with VL are profoundly altered. These changes correlate with levels of serum cytokines and the inflammation marker C-reactive protein. We also fitted univariate and multivariate ordinal logistic regression models to demonstrate the ability of IgG Fc N-glycosylation features and immunity regulators present in serum to predict disease severity in VL patients. Importantly, we show that Fc N-glycosylation profiles change after treatment of VL. This study introduces important concepts contributing to the understanding of antibody responses in infections with Leishmania parasites and provides new insights into the pathology of human VL.

O-30: Long-term efficacy of adalimumab in paediatric patients with Crohn’s disease

O-30: Long-term efficacy of adalimumab in paediatric patients with Crohn’s disease

Does fecal calprotectin predict short-term relapse after stopping TNFα-blocking agents in inflammatory bowel disease patients in deep remission?

This prospective multicenter study examined whether elevated fecal calprotec tin (FC) concentrations after stopping TNFα-blocking therapy can predict clinical or endoscopic relapse. In addition, we evaluated the impact of histological remission on the relapse risk. We enrolled inflammatory bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (< 100 μg/g) remission after a minimum 11 months of TNFα-blocking therapy. The patients were followed-up for 12 months after the discontinuation of TNFα-blocking therapy. FC was collected monthly for the first 6 months and thereafter every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at the study end, and at the time of clinical relapse. Of 52 enrolled patients, 49 (16 Crohn's disease, 33 ulcerative colitis/IBD unclassified) provided the stool samples requested and comprised the study group. During the follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients relapsing showed constantly elevated FC levels for a median of 94 (13-317) days before the relapse. Significant increase in median FC levels was seen 2 (p = 0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse. Constantly normal FC concentrations during the follow-up were highly predictive for clinical and endoscopic remission. Normal FC concentrations in patients with remission were associated with histological remission. FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.

Mo1219 Adalimumab Achieves Efficacy in Mucosal Healing Regardless of Baseline Disease Severity in Patients With Crohn's Disease: Data From EXTEND

68% had inflammatory (B1) disease behavior; 30% had prior resections. Over 7 years, 117 pts completed, while 478 discontinued (36% due to AEs; 28% due to pt decision; 17% due to no improvement/disease deterioration). Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% during years 1 7, respectively. Over 71% of pts were exposed to CZP for >1 year; the average number of CZP injections was 41. No new safety signals were identified during this study. The most common AE was CD exacerbation (30%); most common OI was herpes simplex (3.4%). The observed annual remission rates ranged from 68% 76% (Year 1 to 7, table). The remission rates analyzed by LOCF and NRI methods were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7, respectively. FC levels had no trends toward change; CRP levels were relatively stable. The geometric mean CZP plasma concentrations ranged from 6 10 ug/mL up to year 6; CZP concentrations were typically lower in pts who were anti-CZP antibody positive vs. negative throughout the study (e.g. 3μg/ml vs. 9μg/ml at Wk 54, 3μg/ml vs. 10μg/ml at Wk 210, respectively). Conclusions: The P3 study demonstrates that the long-term safety of CZP is consistent with short-term studies.[1, 2] Additionally, the observed rates of clinical remission were sustainable for 7 years. PRECiSE3 Remission Rates Over 7 Years, observed cases

1055 Recommendations for Creating a High Quality Endoscopy Report for Inflammatory Bowel Disease Patients: Results From a RAND-Appropriateness Panel

G A A b st ra ct s for Crohn's Disease (SES-CD). In UC or IBDU, clinical and endoscopic relapse was defined by Mayo score. Results: Forty-nine patients (16 CD, 33 UC/IBDU) provided the requested stool samples and comprised the study group. Of the 49 patients 15 (31%, 4 CD [25%], 11 UC/IBDU [33%]) relapsed during the one year follow-up and 34 (69%, 12 CD [75%], 22 UC/IBDU [66%]) remained in remission. Significant increase in median FC levels was seen two (120 μg/g, 0-1867, n = 15, p = 0.0014), four (108 μg/g, 7-650, n = 8, p = 0.0056), and six (120 μg/g, 0-431, n = 6, p = 0.0029) months before the actual relapse. In contrast to those with sustained endoscopic remission, patients relapsing showed constantly elevated FC levels. A cutoff of > 140 μg/g (ROC analysis) predicted relapse with a 79% specificity and a 53% sensitivity. At the moment of clinical and endoscopic relapse 4 out of 15 patients (27%, 1 CD, 3 UC) had FC < 100 μg/g. Interestingly, no difference was found in the relapse rates in patients with FC concentration under 50 or 50-100 at baseline, (p = 0.325) nor in patients with or without acute or chronic inflammatory infiltrate in biopsy specimens at baseline (p = 0.221). No significant difference was seen in median FC levels in patients having endoscopic remission and those with mild endoscopic activity at follow-up colonoscopies. Conclusion: FC seems to rise and remain elevated before the actual clinical or endoscopic relapse, suggesting that FC can be used as a surrogate marker for predicting relapse in patients with IBD, and to identifying patients requiring a close follow-up in clinical practice.

Mapping of Crohn's disease outcomes to faecal calprotectin levels in patients maintained on biologic therapy

BackgroundFaecal calprotectin (FC) is a sensitive marker of intestinal mucosal inflammation. The gold standard in Crohn's disease management is mucosal healing. The role of FC to support clinical practice in...

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease

BackgroundFaecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation. AimTo determine whether higher FC levels in individuals with quiescent Crohn's disease are associated with clinical relapse over the ensuing 12months. MethodsA single centre prospective study was undertaken in Crohn's disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12months, based on FC at baseline, was calculated. Kaplan–Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse. ResultsOf 97 patients recruited, 92 were either followed up for 12months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12months. Median FC was lower for non-relapsers, 96μg/g (IQR 39–237), than for relapsers, 414μg/g (IQR 259–590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240μg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC≥240μg/g was associated with likelihood of relapse by 12-months 12.18 (95%CI 2.55–58.2) times higher than lower values (p=0.002). ConclusionsIn this prospective dataset, FC is a useful tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12months. FC of 240μg/g was the optimal cutoff in this cohort.

P571 Adalimumab maintains remission for up to 4 years in patients with ulcerative colitis

68% had inflammatory (B1) disease behavior; 30% had prior resections. Over 7 years, 117 pts completed, while 478 discontinued (36% due to AEs; 28% due to pt decision; 17% due to no improvement/disease deterioration). Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% during years 1 7, respectively. Over 71% of pts were exposed to CZP for >1 year; the average number of CZP injections was 41. No new safety signals were identified during this study. The most common AE was CD exacerbation (30%); most common OI was herpes simplex (3.4%). The observed annual remission rates ranged from 68% 76% (Year 1 to 7, table). The remission rates analyzed by LOCF and NRI methods were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7, respectively. FC levels had no trends toward change; CRP levels were relatively stable. The geometric mean CZP plasma concentrations ranged from 6 10 ug/mL up to year 6; CZP concentrations were typically lower in pts who were anti-CZP antibody positive vs. negative throughout the study (e.g. 3μg/ml vs. 9μg/ml at Wk 54, 3μg/ml vs. 10μg/ml at Wk 210, respectively). Conclusions: The P3 study demonstrates that the long-term safety of CZP is consistent with short-term studies.[1, 2] Additionally, the observed rates of clinical remission were sustainable for 7 years. PRECiSE3 Remission Rates Over 7 Years, observed cases

P393 Patient-reported symptom measures differ in their association with mucosal healing in adults with moderately to severely active ulcerative colitis: Results from ULTRA 1 and 2

68% had inflammatory (B1) disease behavior; 30% had prior resections. Over 7 years, 117 pts completed, while 478 discontinued (36% due to AEs; 28% due to pt decision; 17% due to no improvement/disease deterioration). Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% during years 1 7, respectively. Over 71% of pts were exposed to CZP for >1 year; the average number of CZP injections was 41. No new safety signals were identified during this study. The most common AE was CD exacerbation (30%); most common OI was herpes simplex (3.4%). The observed annual remission rates ranged from 68% 76% (Year 1 to 7, table). The remission rates analyzed by LOCF and NRI methods were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7, respectively. FC levels had no trends toward change; CRP levels were relatively stable. The geometric mean CZP plasma concentrations ranged from 6 10 ug/mL up to year 6; CZP concentrations were typically lower in pts who were anti-CZP antibody positive vs. negative throughout the study (e.g. 3μg/ml vs. 9μg/ml at Wk 54, 3μg/ml vs. 10μg/ml at Wk 210, respectively). Conclusions: The P3 study demonstrates that the long-term safety of CZP is consistent with short-term studies.[1, 2] Additionally, the observed rates of clinical remission were sustainable for 7 years. PRECiSE3 Remission Rates Over 7 Years, observed cases

Evaluation of Crohn’s disease activity: Initial validation of a magnetic resonance enterography global score (MEGS) against faecal calprotectin

To develop an MRI enterography global score (MEGS) of Crohn's disease (CD) activity compared with a reference standard of faecal calprotectin (fC), C-reactive protein (CRP) and Harvey-Bradshaw index (HBI). Calprotectin, CRP and HBI were prospectively recorded for 71 patients (median age 33, male 35) with known/suspected CD undergoing MRI enterography. Two observers in consensus scored activity for nine bowel segments, grading mural thickness, T2 signal, mesenteric oedema, T1 enhancement and pattern, and haustral loss. Segmental scores were multiplied according to disease length. Five points each were added for lymphadenopathy, comb sign, fistulae and abscesses to derive the MEGS. A previously validated MRI CD activity score (CDAS) was also calculated. MRI scores were correlated with clinical references using Spearman's rank. A logistic regression diagnostic model was built to discriminate active (fC > 100 μg/g) from inactive disease. MEGS and CDAS were significantly correlated with fC (r = 0.46, P < 0.001) and (r = 0.39, P = 0.001) respectively. MEGS correlated with CRP (r = 0.39, P = 0.002). The model for discriminating active from inactive disease achieved an area under the receiver-operating curve of 0.75 and 0.66 after leave-one-out analysis. A magnetic resonance enterography global score (MEGS) of CD activity correlated significantly with fC levels. • Magnetic resonance imaging is now widely used to assess Crohn's disease. • Existing MRI activity scores depend on local segmental endoscopic/histological reference standards. • Scores including assessment of disease extent/complications better demonstrate full disease burden. • This new global Crohn's disease burden score correlates with calprotectin and CRP. • The MRI enterography score of disease activity can complement existing clinical markers.

A new rapid test for fecal calprotectin predicts endoscopic remission and postoperative recurrence in Crohn's disease

IntroductionFecal calprotectin (FC), as determined by the enzyme-linked immunoassay (ELISA) test, has been proposed as a promising biomarker of endoscopic activity in Crohn's disease (CD). However data on its accuracy in predicting endoscopic remission according to location and postoperative recurrence (POR) is scarce.Our objective was to evaluate the ability of FC determined by a new quantitative point-of-care test (FC-QPOCT) to predict endoscopic remission and POR in CD patients. MethodsFC was determined simultaneously by an enzyme-linked immunoassay test (FC-ELISA) and a FC-QPOCT in CD patients undergoing colonoscopy. Clinical disease activity was assessed according to the Crohn's Disease Activity Index (CDAI). Endoscopic results were assessed according to the Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) and postoperative recurrence according to the Rutgeerts' score. ResultsA total of 115 ileocolonoscopies were performed (29 on patients with ileocolonic resection). FC levels correlated more closely with the CDEIS than leucocytes, platelets or CRP. The prediction of “endoscopic remission” (CDEIS<3), using FC-QPOCT (cut-off 272μg/g) and FC-ELISA (cut-off 274μg/g) presented an AUC of 0.933 and 0.935 respectively. FC-QPOCT results correlated better with endoscopic activity in the ileocolonic location (Pearson's correlation, r=0.879; P<0.001), than the colonic (r=0.725; P<0.001) or the ileal location (r=0.437; P=0.016). Median FC-QPOCT levels discriminated Rutgeerts' score i0–i1 from i2–i4 (98 (range 30–306)μg/g vs. 234.5 (range 100–612)μg/g respectively, P=0.012). ConclusionsFC determined by rapid quantitative test predicts “endoscopic remission” and endoscopic postoperative recurrence in CD patients.

PTH-094 Faecal Calprotectin Testing in Primary and Secondary Care – are the Current Manufacturer’S Cut-Off Levels Clinically Useful?

IntroductionFaecal Calprotectin (FC) is a protein complex found in high concentrations in neutrophils and is released within the bowel when inflammation occurs. It can be measured quantitatively using ELISA and...

PTU-081 Are we Exposing Patients with a Mildly Elevated Faecal Calprotectin to Unnecessary Investigations?

IntroductionFaecal calprotectin (FC) is increasingly used as a non-invasive marker to differentiate irritable bowel syndrome (IBS) from inflammatory bowel disease (IBD). However, it is a non-specific marker of luminal inflammation...

P252 Efficacy and safety of a split-dose dual-action, low-volume bowel preparation for colonoscopy: the SEE CLEAR I study

we aimed to determine whether FC levels in patients with established CD were predictive of disease progression. Methods: The Edinburgh Faecal Calprotectin Registry (EFCR) comprises data on 22,130 FC assays in 16,278 patients from 2005 2012. Detailed phenotypic information was obtained on patients with CD by retrospective casenote review. Data collected included demographics, disease location, disease behaviour over time, CD-related surgery, investigations, hospitalisations and drug therapy. Patients were included in the main analysis if they had at least 12 months’ follow-up since first FC. The a priori primary endpoint was a composite of progression in Montreal luminal behaviour, hospitalisation for flare and resectional surgery. Results: There were 801 CD patients identified with at least one FC, of which 650 had at least one year’s follow-up, representing 28,121 patient-months of follow-up. The median age was 28y (IQR 20 42) at diagnosis and 40y (28 53) at time of first FC. 211 patients reached the primary endpoint, of whom 57 had had progression of their Montreal behaviour from B1 to B2 or B3, or from B2 to B3. The median of the earliest FC was significantly higher in the group that reached the primary endpoint at 595mg/g (IQR 21

Microbial Contamination in Vegetables at the Farm Gate Due to Irrigation with Wastewater in the Tamale Metropolis of Northern Ghana

The rational for this study was to assess the microbial quality of fresh vegetables at the farm gate of the Water Works road vegetable farm at Gumbihini in the Tamale Metropolis. A total of thirty-six (36) vegetables comprising lettuce, amarantus and cabbages and eight (8) wastewater samples were collected at random and analysed for a period of four months, to assess the microbial contamination level. Samples were analysed for total coliforms, faecal coliforms, E. coli and helminthes eggs. All vegetables sampled during the study period recorded high levels of total and faecal coliform bacteria. Mean faecal coliforms for the various vegetables were as follows; lettuce 3.7 ± 0.5 CFU.g-1, amarantus 3.5 ± 0.6 CFU.g-1 and cabbage 3.1 ± 0.6 log CFU.g-1 fresh weight. FC levels were above the International Commission on Microbiological Specifications for Foods (ICMSF) recommended level of 3 log CFU.g-1 fresh weight. E. coli were recorded in lettuce (3.3 ± 0.6 log CFU.g-1 fresh weight) and amarantus (0.6 ± 0.1 log CFU.g-1 fresh weight) but not in cabbages. Lettuce generally recorded high levels of microbial contamination because of the large surface area occupied by its leaves. Two helminth eggs (Strongiloides stercoralis) were identified in lettuce while four (Ascaris lumbricoides) were identified in wastewater. Microbial loads recorded in wastewater were generally higher than that of vegetables. Since most of these vegetables are eaten fresh or slightly cooked, there is course for concern as public health will be adversely affected. Education of farmers and consumers on food safety has to be intensified to avert a possible outbreak.

Faecal Calprotectin as Reliable Non-invasive Marker to Assess the Severity of Mucosal Inflammation in Patients with Ulcerative Colitis

Background and study aim: We aimed to evaluate the validity and accuracy of the faecal calprotectin in differentiating patients with IBD from those with IBS and in the assessment of the severity of intestinal mucosal inflammation in patients with ulcerative colitis (UC) which may facilitate in the prognosis and follow. Patients and Methods: We studied 60 Patients who came to endoscopy unit with lower gastroenterological symptoms. Patients with history of infections, malignancy, gastrointestinal surgery, pregnancy, alcohol abuse or taking nonsteroidal anti-inflammatory drugs were excluded from study. All patients subjected to thorough medical history, simple clinical colitis activity index was determined with a score ˃ 4 indicate active UC, complete blood picture, liver, kidney function tests, ESR, CRP, ANCA were done, a stool sample for FC levels determined by a highly sensitive enzymelinked immunosorbent assay and total colonoscopy with histological examination of intestinal mucosa biopsy were done. The patients divided into 2 groups. Group A: patients with UC, group B: patients with manifestation of irritable bowel syndrome as a control group. Results: There was a high significant difference between individuals with no pathological activity and other degree of mucosal inflammation as regard simple clinical colitis activity index, endoscopic appearance and faecal calprotectin (p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value of faecal calprotectin in diagnosis of UC were 93.5%, 89.7%, 90.6%, and 92.9% respectively. The positive predictive value and negative predictive value of simple clinical colitis activity index for diagnosis of UC were 76.5% and 80.8% respectively. The positive predictive value and negative predictive value of endoscopic appearance for diagnosis of UC were 100%, and 85.3% respectively. There was a high significant difference and positive correlation between faecal calprotectin, score of colonic pathological activity, endoscopic appearance and simple clinical colitis activity index. Conclusion: Faecal calprotectin is highly useful for the diagnosis and disease monitoring of patients with UC as it is easy, non invasive, reliable tool

PTU-106 A prospective single centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease patients

IntroductionFaecal calprotectin (FC) has become an established non-invasive, sensitive marker of intestinal inflammation in Crohn's disease (CD). A single measurement of FC is used in clinical practice to aid decision...

Pulse-Irrigation Enhanced Evacuation and MoviPrep® With Adjunctive Neostigmine and Glycopyrrolate Improve Bowel Preparation for Colonoscopy After Spinal Cord Injury

Results: After induction therapy, 31 patients responded and 24 reached clinical remission. At baseline, HBi was 11 (6.5-17.5), partial Mayo score 8.5 (7.5-9), FC 2060 (1495-5507) μg/g and CRP 13 (6.5-35.5) mg/L. Following induction therapy, indices, FC and CRP declined from baseline levels (p 221 μg/g that number was 9 out of 15 (60%) within the same time period. Clinical activity correlated with FC (Spearman r=0.62, p 221 μg/g after the induction period is associated with a disease incident within the following 24 weeks. The indices, FC and CRP levels decreased significantly from baseline levels among patients responding to infliximab treatment.

Low-Dose Maintenance Therapy With Infliximab Prevents Postsurgical Recurrence of Crohn's Disease

Infliximab might prevent postsurgical recurrence of Crohn's disease. However, it is unclear whether long-term therapy is necessary and whether alternative strategies could be applied to minimize potential side effects and reduce the costs of treatment. We performed a prospective cohort study in 12 consecutive patients, treated immediately after surgery with maintenance infliximab (5 mg/kg), who did not have clinical or endoscopic evidence of disease recurrence after 24 months; they were followed up for an additional year. Infliximab treatment was then discontinued; patients with disease recurrence, based on endoscopy (Rutgeerts score, >or=2), were given lower doses of infliximab (starting with 1 mg/kg) to re-establish mucosal integrity. Surrogate markers of disease activity (fecal calprotectin [FC], C-reactive protein, and erythrocyte sedimentation rate) were assessed after each infliximab dose. None of the patients had clinical or endoscopic recurrence of Crohn's disease 3 years after surgery. However, discontinuation of infliximab caused endoscopic recurrence after 4 months in 10 of 12 patients (83%). All 10 patients then were treated again with infliximab, which, at a dose of 3 mg/kg every 8 weeks, restored and maintained mucosal integrity for 1 year. Among the surrogate markers, FC levels correlated with endoscopic scores (Wald test, P < .0001). Long-term maintenance therapy with infliximab is required to maintain mucosal integrity in patients after surgery for Crohn's disease. However, a dose of 3 mg/kg (a 40% reduction from the standard dose) was sufficient to avoid disease recurrence, determined by endoscopy, in all patients at 1 year. FC levels correlate with mucosal status at different infliximab doses.

Variability, Seasonality, and Persistence of Fecal Coliform Bacteria in a Cold-Region, Urban Stream

Fecal coliform FC analyses were conducted on weekly water samples collected from a single watershed over a 2-year period in Anchorage, Alaska. Although peak FC concentrations 100 FC/100 mL were observed primarily during the warmer months, lower FC levels 20 FC/100 mL could be observed throughout the year in the urbanized portion of the watershed. Me- dian annual FC counts ranged from 3 FC/100 mL at an undeveloped site to 49 FC/100 mL at one of the urbanized sites. Median FC concentrations were found to be significantly higher in the summer compared to the winter at two locations directly downstream from a lake p=0.011 and 0.029, but not at the sites up- stream or distant from the lake. FC-discharge relationships indicated a significant negative correlation between FC concentration and discharge at two sites p =0.030 and 0.035 and no significant correlation at the remaining three sites. In total, the results indicated that the water quality was impacted not only by peak