Quantification of mucosal EEC in jejunum. A comparative study of IBS patients and healthy controls

Abstract

Background: Enteroendocrine cells (EEC) have been suggested to have a role in the pathogenesis of irritable bowel syndrome (IBS). Although many studies have analysed possible numeric changes of EEC in IBS, the results differ between different studies. One reason might be due to difficulties in standardising the morphometric method.

Aim: The aim of this study was to compare two different methods for counting EEC in jejunum biopsies from patients with IBS and healthy controls.

Method: Fifty-one patients with IBS and 35 healthy controls were included in the study. Jejunum mucosa was procured using a Watson capsule. Slides were immunostained for serotonin and chromogranin A and then scanned digitally. The morphometry was done by counting cells per high power field (hpf) and per mm² after defining area of the mucosa. The two methods were compared using Bland Altman analysis.

Results: There was no difference in the number of EEC in patients with IBS compared to healthy controls. The number of cells detected by per mm² area of mucosa were higher than number of cells per hpf. Counting EEC per high power field systematically underestimated the number of cells in the mucosal area.

Conclusions: Counting cells per mm² mucosal area gives a better representation of the number of EEC in small bowel mucosa. The finding of no difference in EEC numbers does not imply an equal function and further studies are needed to evaluate the role, if any of EEC, in IBS.     

Association of homocysteine and inflammatory-related molecules in sickle cell anemia

Objective: Investigate the role of homocysteine (Hcy), Th17-related cytokines, and adhesion molecules in the inflammatory state seen in the sickle cell anemia (SCA).

Methods: We studied the Hcy, interleukin (IL)-17, and transforming growth factor β (TGF-β) cytokine levels of 62 SCA patients, as well as the expression levels of inflammatory and endothelial activation markers.

Results: We found significant associations between Hcy levels and increased expression of IL-17 and TGF-β among SCA patients, and a positive significant correlation between Hcy and soluble vascular cellular adhesion molecules (sVCAM). SCA individuals had raised IL-17 levels when compared with controls.

Discussion: These results suggest a possible role of Hyc in the induction of TGF-β and IL-17. Other authors proposed that Hcy may contribute to the initiation and progression of vascular disease by monocyte activation, resulting in the secretion of cytokines that amplify the inflammatory response. The role of Hcy in cytokine production and oxidative stress in the endothelium may explain the increase of sVCAM expression and, the vascular activation currently described among the SCA individuals with the highest Hcy serum levels. The chronic inflammation was observed in hyperhomocysteinemic mice, with an increased expression of VCAM-1 and plasma levels of tumor necrosis factor-alpha, showing an association of this inflammatory molecule and vascular changes.

Conclusion: Our findings suggest that the increased levels of IL-17,Hcy and sVCAM contributes contributes to the vascular inflammation and activation presented by SCA patients, which probably have an important role in vaso-occlusion. On the basis of the presented data, IL-17 and Hcy might be considered as important components in the pathogenesis of SCA.     

Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome

Objective: Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients.

Methods: Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included. A standard colonoscopy was performed in both the patients and controls, and biopsy samples were taken from the colon and the rectum. The biopsy samples were stained with hematoxylin–eosin and immunostained for CgA. The density of CgA cells was determined by computerized image analysis.

Results: In the colon and rectum, the CgA cell densities were far higher in both IBS and healthy Thai subjects than in Norwegians. The colonic CgA cell density was lower in Norwegian IBS patients than in controls, but did not differ between Thai IBS patients and controls. In the rectum, the CgA cell densities in both Thai and Norwegian patients did not differ from those of controls.

Conclusions: The higher densities of CgA cells in Thai subjects than Norwegians may be explained by a higher exposure to infections at childhood and the development of a broad immune tolerance, by differences in the intestinal microbiota, and/or differing diet habits. The normal CgA cell density in Thai IBS patients in contrast to that of Norwegians may be due to differences in pathophysiology.     

Biomarkers as a diagnostic tool for irritable bowel syndrome: where are we?

Introduction: Irritable bowel syndrome (IBS) is a common condition in clinical practice. There are currently no objective tests to rule in the disease, but rather tests to rule out other diseases. Biomarkers in IBS may provide the tools needed for diagnosis, prognosis and therapy. These include identification of differences in microbial composition, immune activation, bile acid composition, colonic transit, and alteration in sensation in subgroups of IBS patients.

Areas covered: Studies included in our review were chosen based on a PubMed search for ‘biomarkers’ and ‘IBS’. We have reviewed the literature on biomarkers to appraise their accuracy, validity and whether they are actionable. We have not covered genetic associations as biomarkers in this review.

Expert commentary: There is significant promise in the usefulness of biomarkers for IBS. The most promising actionable biomarkers are markers of changes in bile acid balance, such as elevated bile acid in the stool, and altered colonic transit. However, there is also potential for microbial studies and mucosal proteases as future actionable biomarkers.     

Symptoms in patients with ulcerative colitis in remission are associated with visceral hypersensitivity and mast cell activity

Abstract

Objective. Patients with ulcerative colitis in remission (UCR) frequently report irritable bowel syndrome (IBS)-like symptoms. Recent studies have pointed to the role of mast cells in mediating visceral hypersensitivity in IBS. We hypothesized that visceral hypersensitivity is frequently present in patients with UCR and is related to the quantity and activity of mast cells in the sigmoid mucosa. Material and methods. A group of 17 controls and 19 patients with UCR were studied. Rectal compliance and perception were measured by electronic barostat. Sigmoid biopsies were taken to quantify the amount of mast cells, degranulating mast cells and mast cells in close proximity to mucosal nerve endings. Results. Visceroperception significantly increased in UCR (p < 0.05) versus controls. Rectal perception correlated positively with IBS-like symptoms in UCR (r = 0.969; p < 0.05). The amount of mucosal mast cells (per 100 crypts) was significantly increased in UCR versus controls: 228 ± 20 versus 163 ± 18 (p < 0.05). In the UCR patients a higher percentage of mucosal mast cells was in close proximity to nerve endings (58 ± 4 vs. 38 ± 3% in controls; p < 0.05) or was degranulating (40 ± 7 vs. 16 ± 4% in controls; p < 0.05). There was a significant but weak correlation between quantity of mucosal mast cells and pain perception (r = 0.32; p < 0.05). Conclusion. Rectal hypersensitivity is associated with mucosal presence and activation of mast cells and with IBS-like symptoms in patients with UCR.     

Fructose intolerance in patients with irritable bowel syndrome: a case-control study

"Introduction: Recently it has been reported that prevalence of fructose intolerance (FI) in patients with functional gastrointestinal disorders range between 38% -75%. Objective: To determine the prevalence of FI in subjects diagnosed with irritable bowel syndrome (IBS). Methods: We studied 25 subjects (17 women, average age 36 years) with IBS (Rome II) and 25 healthy controls (14 women, mean age 37 years) who underwent a breath test after oral loading with fructose (Gastrolyzer ?, Bedfont Scientific Ltd., UK). The load consisted of 25 grams of fructose dissolved in 250 ml of water (10% solution). Breath test analysis of the particles per million (ppm) of hydrogen exhaled were performed every 15 minutes for 3 hours. The fructose breath test was considered positive when concentrations of hydrogen were higher than at 20 ppm or a raising greater than 5 ppm in 3 consecutive samples was detected. Results: According to the Rome II criteria, 10 patients (40%) had IBS-C, 9 (36%) had IBS-D and 6 (24%) had IBS-M. Thirteen (52%) of IBS patients had IF, while only 4 (16%) of control subjects (p = 0.01). Patients with IBS and fructose intolerante tend to suffering from diarrhea predominant IBS (p = 0.053). Conclusions: Fructose intolerance may be responsible for gastrointestinal symptoms in at least half of IBS patients, especially in the group of patients with IBS-D."     

Extra Digestive Manifestations of Irritable Bowel Syndrome: Intolerance to Drugs?

Patients with IBS frequently complain of medication side effects. The goals of this study were to assess the prevalence of drug intolerance as an extra GI manifestation in patients with IBS and to verify the association between drug intolerance and psychological comorbidity. Female patients followed in a tertiary care center completed questionnaires assessing the presence of drug intolerance as well as somatic and psychological extra GI conditions. IBS patients (Rome II criteria; n = 71) were compared to inflammatory bowel disease patients (IBD; n = 96) or to healthy controls (HC; n = 67). The relationship to psychological comorbidity was verified in two different paradigms: (1) by looking at the statistical correlation between drug intolerance and the psychological extra GI symptoms in our IBS patients, and (2) by comparing in a meta-analysis the side effects to placebo (the nocebo effect is presumably increased due to hypervigilance or amplification in psychological disorders) in IBS patients or in patients with comparable medical conditions included in various drug trials approved by Health Canada. Our results show that prevalence of drug intolerance was significantly more elevated in IBS (41% patients) than in HC (7%) or in IBD (27%); somatic and psychological extra GI symptoms were also markedly increased in IBS. In addition, drug intolerance in our IBS patients was significantly associated with somatic comorbidities such as fatigue or multiple symptoms (P < 0.001), but not with psychological factors such as depression, anxiety, mood instability, or sleep disorder. A meta-analysis revealed that the nocebo effect was not different in patients with IBS than in control patients. In conclusion, drug intolerance is a frequent extra GI manifestation of IBS that is not associated with psychological comorbidity; thus, a somatic origin must be explored.     

Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects

Abstract

Objective. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. Material and methods. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. Results. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. Conclusions. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.     

腹泻型肠易激综合征患者食物不耐受、症状指数及回盲部肥大细胞变化的相关性

目的:比较食物不耐受(food intolerance,FI)在腹泻型肠易激综合征患者(diarrhea-dominant irritable bowel syndrome,D-IBS)及健康人群中的存在情况,分析D-IBS患者食物不耐受严重程度、症状指数与回盲部肥大细胞数量变化之间的关系,以探讨食物不耐受在D-IBS发病中的意义及可能机制.方法:选取符合罗马Ⅲ诊断标准的D-IBS患者22例为病例组,无消化系症状的健康体检者21例为对照组,分别接受结肠镜检查.应用食物不耐受状况评价问卷对2组进行食物不耐受状况评分;用功能性肠病症状严重指数(functional bowel disorder severity index,FBDSI)和IBS病情尺度调查表(IBS symptomseverity scale,IBS-SSS)对病例组进行IBS症状严重程度评分.所有研究对象均接受结肠镜检查,在距回盲瓣4cm处取活检组织2块,采用甲苯胺蓝染色法计数黏膜肥大细胞数量,并与食物不耐受严重程度指数、IBS症状严重程度评分进行相关性分析.结果:D-IBS患者回盲部肠黏膜肥大细胞计数(4.68±0.55)个/高倍镜视野,健康对照组为(1.33±0.54)个/高倍镜视野,P<0.001,差异具有统计学意义;病例组食物不耐受存在情况明显高于对照组(P<0.05);食物不耐受严重程度与IBS症状严重程度指数间呈正相关(FBDSI:r=0.992,P<0.001;IBS-SSS:r=0.970,P<0.001);回盲部肥大细胞计数与I B S症状严重程度指数间呈正相关(FBDSI:r=0.957,P<0.001;IBS-SSS:r=0.985,P<0.001);食物不耐受严重程度与IBS患者回盲部肥大细胞计数间呈正相关(r=0.964,P<0.001),健康对照组中食物不耐受者回盲部肥大细胞计数明显高于无食物不耐受者(P<0.05).结论:D-IBS临床症状与肠道肥大细胞数量增多密切相关,食物抗原的刺激作用可能是D-IBS患者回盲部肥大细胞数目增多的原因之一;D-IBS患者食物不耐受存在情况普遍,食物不耐受可加重D-IBS患者肠道症状.     

Antiflagellin antibodies suggest infective participation in irritable bowel syndrome pathogenesis

Evaluation of: Schoepfer AM, Schaffer T, Seibold-Schmid B et al. Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients. Neurogastroenterol. Motil. 20(10), 1110–1118 (2008).

Irritable bowel syndrome (IBS) is a functional disorder of multifactorial origin. Recent attention has been paid to the potential role of immune activation in intestinal sensorimotor dysfunction and symptom generation in patients with IBS. The link between immune activation and IBS is further supported by the evidence that IBS may develop after an acute episode of infectious gastroenteritis, IBS-like symptoms may precede the diagnosis or accompany a period of remission of inflammatory bowel disease (IBD), and quantitative histopathologic data demonstrate the presence of low-grade mucosal immune infiltration in a large subset of patients with IBS. These data also suggest some areas of potential overlap between IBS and IBD. The present study explored the possibility that, similarly to IBD patients, IBS patients have antibodies directed against certain components of indigenous flora, such as flagellin (the primary structural component of bacterial flagella). The authors demonstrated that, compared with healthy controls, antibodies against flagellin were recognized more frequently in patients with IBS. Furthermore, these antibodies were found more frequently in postinfectious compared with unspecific IBS. In patients with Crohn’s disease, antiflagellin antibodies were detected with an increased frequency and at higher concentrations than in patients with IBS. All together, these results indicated the presence of a systemic immune activation in IBS patients, characterized by specific antibodies directed against luminal bacterial antigens. Furthermore, these results support the hypothesis that a subset of IBS presents an immune activation with pathogenic features common with IBD.     

感染对IBS患者肠黏膜细胞因子表达的影响

目的:探讨感染对肠易激综合征(irritable bowel syndrome,IBS)患者神经-免疫-内分泌网络的影响.方法:感染后肠易激综合征(postinfectious irritable bowel syndrome,PI-IBS)患者45例,non-PI-IBS患者60例及30例对照者,结肠镜下活检回盲部黏膜标本,采用免疫组织化学法检测其肠黏膜SP、IL-2、IFN-γ、SPR与5-HT的表达,肥大细胞(mast cells,MC)采用甲苯胺蓝染色.结果:PI-IBS患者的SP表达分别高于non-PI-IBS与对照组(t=2.5,2.8,P<0.01);PI-IBS患者的MC表达分别高于non-PI-IBS与对照组(t=11.5,12.1,P<0.01).PI-IBS患者的5-HT表达分别高于non-PI-IBS与对照组(t=13.6,14.1,P<0.01);PI-IBS患者的SPR表达分别高于non-PI-IBS与对照组(t=3.8,6.1,P<0.05);PI-IBS患者的IFN-γ表达分别高于non-PI-IBS与对照组(t=13.8,15.2,P<0.05);PI-IBS患者的IL-2表达分别高于non-PI-IBS与对照组(t=12.6,14.7,P<0.05).PI-IBS患者回盲部黏膜MC和SP的表达呈高度正相关(r=0.71,P<0.01).PI-IBS患者回盲部黏膜5-HT和SPR的表达呈密切相关(r=0.18,P<0.05).IFN-γIL-2阳性表达的PI-IBS患者,SP表达高于非PI-IBS组(r=2.2,2.3,P<0.05)和对照组(t=2.3,2.4,P<0.05).结论:肠道感染后,神经纤维在IBS的免疫-神经-内分泌发生机制中的作用至关重要.     

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model

Objective: Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model.

Materials and methods: NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined.

Results: PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO?/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO?/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group.

Conclusions: Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.     

Association of irritable bowel syndrome and venous thromboembolism

Objective: Inflammatory bowel disease (IBD) is associated with venous thromboembolism (VTE). Whether functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), are associated with VTE has not been determined. This nationwide study aimed to determine the risk of VTE in IBS outpatients in primary and specialist care.

Design: We performed two matched case-control studies. Cases (n?=?90,502) were individuals in Sweden aged 18–80 years with a first hospital diagnosis of VTE between 2001 and 2010. Five controls (n?=?452,510) from the Swedish Total Population Register were matched to each case for birth, sex, country of birth, and education level. Diagnosis of IBS was determined in the Swedish hospital outpatient register. This procedure was replicated for the primary care population. As the Primary Care data did not have nationwide coverage, we only included individuals that were registered in the Primary Care database. A total of 9766 cases of hospital diagnosed VTE individuals could be found in the Primary Care population and they were matched to 48,830 controls also from the Primary health care population. Conditional logistic regression was used to determine odds ratio (OR) for first VTE diagnosis.

Results The adjusted OR for VTE when IBS was diagnosed in hospital outpatient care was 1.49 (95% confidence interval 1.33–1.67). The crude OR for VTE was 1.18 (0.94–1.48) when IBS was diagnosed in primary care.

Conclusions: This is the first study describing an association between VTE and IBS. The results suggest that specialist treated IBS patients have increased risk of VTE.     

Fructose intolerance in IBS and utility of fructose-restricted diet

INTRODUCTION: Whether dietary fructose intolerance causes symptoms of irritable bowel syndrome (IBS) is unclear. We examined the prevalence of fructose intolerance in IBS and long-term outcome of fructose-restricted diet. METHODS: Two hundred and nine patients with suspected IBS were retrospectively evaluated for organic illnesses. Patients with IBS (Rome II) and positive fructose breath test received instructions regarding fructose-restricted diet. One year later, their symptoms, compliance with, and effects of dietary modification on lifestyle were assessed using a structured interview. RESULTS: Eighty patients (m/f=26/54) fulfilled Rome II criteria. Of 80 patients, 31 (38%) had positive breath test. Of 31 patients, 26 (84%) participated in follow-up (mean=13 mo) evaluation. Of 26 patients, 14 (53%) were compliant with diet; mean compliance=71%. In this group, pain, belching, bloating, fullness, indigestion, and diarrhea improved (P<0.02). Of 26 patients, 12 (46%) were noncompliant, and their symptoms were unchanged, except belching. The mean impact on lifestyle, compliant versus noncompliant groups was 2.93 versus 2.57 (P>0.05). CONCLUSIONS: About one-third of patients with suspected IBS had fructose intolerance. When compliant, symptoms improved on fructose-restricted diet despite moderate impact on lifestyle; noncompliance was associated with persistent symptoms. Fructose intolerance is another jigsaw piece of the IBS puzzle that may respond to dietary modification.     

Irritable Bowel Syndrome on Inflammatory Bowel Disease in Deep Remission: No Relation with Remission Deepening and Inflammation

Background: The aim of the study was to establish the frequency of irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in clinical, endoscopic, and histologic remission and in relation to both the depth of remission and inflammation markers. Methods: Patients with ulcerative colitis (UC) and with Crohn’s disease (CD) in clinical remission for at least 6 months were enrolled in the study. All of the patients underwent colonoscopy, and biopsy specimens were taken to evaluate endoscopic and histopathologic remission. Patients were evaluated according to Rome III criteria for IBS. Fecal calprotectin level and blood samples for C-reactive protein (CRP), sedimentation rate, and fibrinogen levels were studied.Results: IBS frequency was 20.9% in UC cases and 28.9% in CD cases in clinical remission. Rates with and without endoscopic remission in UC (20.5% vs. 22.2%, P = .727) and CD (25% vs. 33.3%, P = .837, respectively) were not different. Similarly, rates with and without histopathologic remission in UC (15.7% vs. 26.6%, P = .723), and CD (21.4% vs. 33.3%, P = .999) were not statistically different. Also, it was not related to inflammation markers.Conclusion: IBS frequency among IBD patients with remission was in a substantial rate; these rates kept up with the process of deep remission and even complete mucosal healing and were irrelevant to inflammation.     

Decreased expression of thymic stromal lymphopoietin in salivary glands of patients with primary Sjögren’s syndrome is associated with increased disease activity

Objectives: Thymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory cytokine involved in Th2- and Th17-mediated immune responses in different autoimmune diseases. TSLP expression in relation to disease activity was studied in salivary glands of primary Sjögren’s syndrome (pSS) patients as compared to non-SS sicca (nSS) controls.

Methods: Tissue sections of minor salivary glands from pSS and nSS patients were stained with monoclonal antibodies against human TSLP, CD3, CD19 and cytokeratin high molecular weight (CK HMW) or stained for Alcian blue to detect mucus production. The number of TSLP-expressing cells was quantified and expression was correlated to local and systemic disease parameters.

Results: The number of TSLP-expressing cells was significantly lower in pSS patients than in nSS controls and correlated with a range of disease markers. In pSS patients, TSLP was expressed outside of lymphocytic infiltrates at sections that also encompassed high numbers of intact acinar cells. This difference was independent of tissue destruction.

Conclusions: Reduced TSLP expression in pSS patients is associated with increased local and systemic inflammatory markers. Loss of TSLP expression may contribute to Th1/Th17-associated immunopathology in pSS, in line with previous studies demonstrating that TSLP promotes a protective Th2 milieu at mucosal sites.     

Circulating levels of cytokines are increased in restless legs syndrome

Background

Restless legs syndrome [RLS] is known as a disease of iron and dopaminergic dysregulation but inflammatory processes might also have a role in the pathogenesis. In this study, we compared the circulating levels of hsCRP, IL-1β, IL-6, and TNF-α in patients with primary restless legs syndrome [RLS] and healthy control subjects.

Methods

We prospectively included 29 patients with primary RLS and 65 healthy controls [HC], all age-sex matched. The diagnosis of RLS was established using international guidelines. IRLSSG Severity Scale was used to evaluate the severity of RLS. Plasma levels of hsCRP, IL-1β, IL-6, and TNF-α were measured in all participants.

Results

The mean age of patients was 37.8?±?11.3 and 52% of RLS group were women. Serum IL-1β, IL-6, and TNF-α levels of the patient group were statistically significantly higher compared to HC [p?<?0.001 for all variables]. Plasma levels of hsCRP did not differ between groups. There were 8 patients with mild RLS [28%], 13 patients with moderate RLS [45%], and 8 patients with severe RLS [28%]. Only IL-6 values were significantly different between the groups. In the severe group, the value of IL-6 was significantly higher than in the other groups [p: 0.03].

Conclusion

These results showing higher circulating levels of inflammatory cytokines in patients with RLS support the notion that inflammation may be involved in the pathogenesis of primary RLS. However, it is necessary to perform further studies to determine if this finding is a cause or an effect.

     

Imbalance of Th17, Treg,and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA.

Methods

A total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4⁺, CD19⁺ B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( −) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA).

Results

Patients with RA had higher percentages of CD4⁺ T, CD19⁺ B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF⁺ or ACPA⁺ patients exhibited elevated percentages of CD19⁺ B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF⁻/ACPA⁻ and RF⁺/ACPA⁺ patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different.

Conclusion

Th17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA.

This month in Scandinavian Journal of Gastroenterology

Abstract

Objectives: Use of antibiotics affects the composition of the gut microbiome. The microbiome is thought to play a role in development of irritable bowel syndrome (IBS), but antibiotics as a possible risk factor for IBS has not been clarified. We aimed to explore if antibiotics is a risk factor for IBS by investigating use of antibiotics and development of IBS in a cohort from the Danish background population.

Materials and Methods: An internet-based web panel representative of the Danish background population was invited to participate in a survey regarding the epidemiology of IBS in 2010, 2011 and 2013. A questionnaire based on the Rome III criteria for IBS were answered at all three occasions. In 2013, a question regarding use of antibiotics in the past year was included.

Results: In 2013, use of antibiotics was reported by 22.4% (624/2781) of the population. A higher proportion of individuals with IBS reported use of antibiotics compared with asymptomatic controls [29.0% (155/534) vs. 17.9% (212/1,184), p?Conclusions: Antibiotics is a risk factor for IBS in asymptomatic individuals. Possible mechanisms should be investigated in future studies.