Gülen Arslan Lied

Functional and Clinical Aspects of the B-Cell-Activating Factor (BAFF): A Narrative Review

B‐cell‐activating factor (BAFF) influences peripheral B‐cell survival, maturation and immunoglobulin class‐switch recombination and has a range of potential clinical implications. Biological functions of BAFF and its relevance in various clinical disorders including currently investigated BAFF‐targeting therapies are reviewed and discussed based on PubMed search of relevant articles. Serum levels of BAFF are increased in autoimmune diseases including autoimmune hepatitis and primary biliary cirrhosis where BAFF concentrations are related to titres of autoantibodies and disease progression. Increased BAFF levels are found in synovial, bronchoalveolar and gut lavage fluids, suggesting local class switching and immunoglobulin production. Clinical relevance and diagnostic potential of BAFF are also noted in patients with allergic diseases, malignancies and infections including hepatitis C virus. BAFF antagonists are promising new therapeutic agents, currently being tried in B‐cell‐related autoimmune diseases. Serum level of BAFF may indicate disease mechanisms and the degree of activity. Determination of BAFF in different body compartments like synovium, airways and gut may also have clinical implications. Results of ongoing clinical trials with BAFF antagonists are eagerly awaited.

Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is increasingly recommended for patients with irritable bowel syndrome (IBS). We aimed to investigate the effects of a blinded low‐FODMAP vs high‐fructo‐oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short‐chain fatty acids (SCFAs).

Clinical and surgical recurrence of Crohn's disease after ileocolonic resection in a specialist unit.

Background Postoperative clinical and endoscopic recurrence is common in Crohns disease. Aim We aimed to assess postoperative recurrence and management in a cross-sectional patient cohort in one specialist unit, before the introduction of a uniform postoperative preventive strategy. Methods Review of patients who had an ileocolonic resection for Crohns disease between 2002 and 2005 in a secondary and tertiary care specialist centre. Results Ninety-nine patients (42 male; 57 female; mean age, 37 years) with a median disease duration of 10 years, were reviewed. Indications for surgery were obstruction (n=61), failed medical therapy (n=31) and internal fistula(e) (n=7). Thirty patients (30%) were active smokers at the time of resection. Fifty patients (51%) had at least one previous Crohns resection. Clinical and surgical recurrence rates were 28 and 5%, respectively, at 1 year. All five patients had the same indication for their further surgery as for their index operation (four fistulizing or stricturing). Median time to clinical recurrence was 10 months in those with recurrence. Nineteen percent of patients had an ileocolonoscopy at a median of 6 months after surgery, and 60% had been reviewed by a gastroenterologist, after surgery. Clinical recurrence occurred in nine of 28 (32%) without and 19 of 71 with (26%) postoperative medical therapy (P=NS). Conclusion Postoperative recurrence of Crohns disease was high in the short term. The indication for repeat surgery stayed true within patients. Prospective treatment strategies, based on recent trial evidence, are needed to diminish postoperative recurrence.

Predictive value and clinical significance of myenteric plexitis in Crohn's disease

Background: Recurrence of Crohns disease (CD) after ileal or colonic resection is common. Myenteric plexitis in the proximal resection margin of an ileocolonic CD resection specimen may indicate ongoing pathology that relates to disease recurrence. We assessed risk factors for myenteric plexitis, the effect of plexitis on clinical recurrence, and whether preoperative medical therapies affect the intensity of plexitis. Methods: Ileocolonic resection specimens from 99 patients with CD were histologically scored for the presence and severity of plexitis. Myenteric plexitis was correlated with immunosuppressive therapy before index surgery. Univariate and multivariate analyses were performed to identify predictive factors for plexitis. Results: Myenteric plexitis was present in 43% and 85% of cases in the proximal resection margin and the affected resected segments of CD, respectively. Patients with a previous resection were more likely to have plexitis than those with no previous resection (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.21–10.15, P = 0.02), and those with a greater duration of disease were less likely to have plexitis in the proximal resection margin (OR 0.68, 95% CI 0.48–0.96, P = 0.03). Preoperative immunosuppressive therapy was not associated with a lesser incidence of plexitis. Twelve of 40 (30%) patients with plexitis and 9 of 54 (16%) patients without plexitis in the proximal resection margin subsequently developed clinical recurrence (median 10 months; P = 0.17). Conclusions: Previous resections and shorter disease duration are associated with plexitis in proximal resection margin of CD. The prognostic value of plexitis in postoperative disease recurrence and risk stratification remain to be prospectively established. (Inflamm Bowel Dis 2009)

Anxiety and depression in patients with self-reported food hypersensitivity

OBJECTIVE Self-reported food hypersensitivity (SFH) is common. Psychological factors are assumed to be associated. We assessed anxiety and depression in SFH patients, using both questionnaires and interview. METHODS Consecutive patients (n=130) and randomly selected healthy volunteers (n=75) completed the Hospital Anxiety and Depression Scale (HADS), the neuroticism scale of the Eysenck Personality Questionnaire (EPQ-N) and the General Health Questionnaire (GHQ). Seventy-six of the patients were also interviewed by use of the Mini International Neuropsychiatric Interview and the Montgomery-Aasberg Depression Rating Scale. All patients underwent extensive allergological, gastroenterological and dietary examinations. RESULTS According to interviews, 57% of patients fulfilled the DSM-IV criteria for at least one psychiatric disorder. Anxiety disorders (34%) and depression (16%) predominated. According to questionnaires, patients scored significantly higher than controls on all psychometric scales except for depression (HADS). We also found an underreporting of depression in HADS compared with interviews (2.5% vs. 16%, P=.001). Food hypersensitivity was rarely confirmed by provocation tests (8%). Eighty-nine percent of the patients had irritable bowel syndrome. CONCLUSIONS Anxiety and depression are common in patients with IBS-like complaints self-attributed to food hypersensitivity. Anxiety disorders predominate. In this setting, depression may be underreported by HADS.

Do psychological factors predict symptom severity in patients with subjective food hypersensitivity

Abstract Objective. We examined whether psychological factors such as general and gastrointestinal symptom-specific anxiety and depression could predict symptom severity in patients with unexplained, self-reported (subjective) food hypersensitivity. For the purpose, we translated and validated the Visceral Sensitivity Index (VSI). Material and methods. Seventy consecutive patients completed questionnaires for Hospital Anxiety and Depression Scale, VSI, Irritable Bowel Syndrome Symptom Questionnaire, and Subjective Health Complaints Inventory. Relationship between scores on psychological factors and scores on somatic symptoms were studied by multiple regression analyses. Results. Most patients reported non-gastrointestinal symptoms in addition to their irritable bowel syndrome complaints, but general and symptom-specific anxiety, and depression could not explain a significant amount of the variance in somatic complaints. Gastrointestinal symptom-specific anxiety was a significant predictor of gastrointestinal complaints (p = 0.02), and age was the sole significant predictor of non-gastrointestinal complaints (p = 0.01). Approximately 90% of the total variance in symptom severity remained unexplained by the psychological factors. The Norwegian version of the VSI had satisfactory validity (Cronbach alfa = 0.93). Symptom-specific and general anxiety were significantly correlated (r = 0.48, p ≤ 0.0001). Conclusions. Psychological factors were not major predictors of symptom severity in patients with subjective food hypersensitivity. The Norwegian version of VSI had satisfactory validity.

Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis

Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS) in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS). Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha) and fecal samples (HemoFEC occult blood) were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS-induced colitis was able to be visualized by transabdominal sonography. Moreover, ultrasound findings, occult blood sampling, and histological findings supported each other, indicating that ultrasonography can be used to assess inflammation in a rat experimental model.

Lifestyle of patients with self-reported food hypersensitivity differ little from controls.

The aim of this study was to examine the lifestyle of adult patients with abdominal discomfort (i.e., diarrhea, bloating, pain, and irregular defecation) self-attributed to food hypersensitivity and compare it with controls to see if the patients had a special lifestyle explaining their symptoms. Forty-six participants in this study were adult ethnic Norwegians referred by general practitioners to the Centre for Occupational and Environmental Allergy at Haukeland University Hospital because of gastrointestinal complaints, which the patients or their doctors suspected could be due to food allergy. They were compared with 70 age- and sex-matched volunteer controls from the general population. All participants filled out an extensive questionnaire focusing on different lifestyle aspects. One hundred percent of the patients and 43% of the controls (p < .0001) reported hypersensitivity to at least one food item. Significantly, fewer patients than controls reported daily consumption of milk (p = .004), coffee (p = .02), and alcohol (p = .008) for the past year. Among consumers, the participants used less milk (P = .002) and coffee (P = .04) than controls. Eating habits, meal patterns, quality of sleep, the amount of exercise, and use of painkillers were similar in both groups. There were small differences in lifestyle between the patients and the controls. Patients with gastrointestinal complaints self-attributed to food hypersensitivity used less milk, coffee, and alcohol, but none of those differences explain their symptoms. Such lifestyle would rather be expected to lessen symptoms, and we postulate that it is the consequence of their food intolerance and not its cause.

The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge

Non‐coeliac gluten‐sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten‐challenge in patients with a symptom‐relief when following a gluten free‐diet (GFD).

Dendritic cell populations in patients with self-reported food hypersensitivity

Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs) were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.