| 1. |
|
|
| 2. |
- Ahluwalia, Bani, et al.
(författare)
-
Effects of Aloe barbadensis Mill. extract (AVH200 (R)) on human blood T cell activity in vitro
- 2016
-
Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 179, s. 301-309
-
Tidskriftsartikel (refereegranskat)abstract
- Ethnopharmacological relevance: Aloe barbadensis Mill. (Aloe vera) is a widely used medicinal plant well reputed for its diverse therapeutic applications. It has been used for thousands of years in folk medicine to treat various conditions and the Aloe vera gel has been reported to possess anti-inflammatory as well as immunostimulatory and immunomodulatory properties. However, the mode of action is still unclear. Aim of the study: The aim of this study was determine the effects of two well-defined A. barbadensis Mill. extracts AVH200 (R) and AVE200 on human blood T cells in vitro. Materials and methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in the presence or absence of AVH200 (R) and AVE200. The T cell phenotype was investigated by flow cytometry, cell proliferation was determined by CFSE dye and thymidine assay, respectively and cytokine secretion was determined by MSD (R) Multi-Spot Assay system and ELISA. Results: The presence of AVH200 (R) resulted in a reduced expression of CD25 among CD3(+) T cells and suppression of T cell proliferation in a dose dependent manner. Furthermore, AVH200 (R) reduced the expression of CD28 on CD3(+) T cells. AVH200 (R) also reduced the secretion of IL-2, IFN-gamma and IL-17A in PBMC cultures. The AVH200 (R) dose dependent reduction in T cell activation and proliferation recorded in the cell cultures was not due to apoptosis or cell death. Additionally, AVH200 (R) was found to be more effective as compared to AVE200 in reducing T cell activation and proliferation. Conclusion: AVH200 (R) has the potential to reduce the activation, proliferation and cytokine secretion of healthy human blood T cells. Our study suggests that AVH200 (R) has a suppressive effect on human blood T cells in vitro.
|
|
| 3. |
- Bennet, Sean, et al.
(författare)
-
Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome
- 2016
-
Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 111:8, s. 1165-1176
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms. METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-gamma and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed. RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-gamma tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified. CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.
|
|
| 4. |
- Dahlén, Rahil, et al.
(författare)
-
Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis
- 2013
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475. ; 78:3, s. 275-284
-
Tidskriftsartikel (refereegranskat)abstract
- Many patients with inflammatory bowel disease (IBD) are undergoing therapy with infliximab, an antibody specific for TNF. However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti-TNF therapy-naive ulcerative colitis (UC) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA, and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD25 in CD4(+) and CD8(+) T cell populations and inhibited secretion of IFN-, IL-13, IL-17A, TNF as well as granzyme A. Infliximab also suppressed CD4(+) and CD8(+) T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen-specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP3(+)CD4(+) T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab-mediated disease remission in patients with UC.
|
|
| 5. |
- Forshammar, Johan, et al.
(författare)
-
A pilot study of colonic B cell pattern in irritable bowel syndrome
- 2008
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 43:12, s. 1461-6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Low-grade gastrointestinal inflammation has been reported in patients with irritable bowel syndrome (IBS). However, the colonic B-cell pattern has not been investigated in these patients. Therefore, the aim of this pilot study was to investigate the distribution and isotype of immunoglobulin-producing B cells in the colonic mucosa of IBS patients. MATERIAL AND METHODS: Patients with IBS (n=12) fulfilling the Rome II criteria were compared with controls (n=11). Immunohistochemical staining of biopsies from the sigmoid and ascending colon was performed. RESULTS: The number of IgA(+) B cells in the ascending colon was lower in IBS patients than in controls (p=0.039). Furthermore, unlike controls, IBS patients had a reduction of IgA(+) B cells in the ascending colon relative to the sigmoid colon (p=0.04). Neither the IgG(+), nor the IgM(+) colonic B-cell numbers differed between IBS patients and controls. Very few colonic IgE(+) cells were detected and there was no difference between the two subject groups. CONCLUSIONS: The reduced number of colonic IgA(+) B cells in IBS patients suggests that the disorder may be associated with a modified gut immune defence. Whether this phenomenon is causally related to symptoms remains unknown and merits further investigation in a larger group of patients.
|
|
| 6. |
- Holmén, Nathalie, 1979, et al.
(författare)
-
CD4+CD25+ regulatory T cells in irritable bowel syndrome patients.
- 2007
-
Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925. ; 19:2, s. 119-25
-
Tidskriftsartikel (refereegranskat)abstract
- The aetiology of the irritable bowel syndrome (IBS) is incompletely understood. A low-grade colonic inflammation is frequently seen, but it is unclear to what extent this phenomenon contributes to the pathophysiology of IBS. CD4(+)CD25(+) regulatory T cells (Treg) are implicated to play an important role in suppressing intestinal inflammation. We, therefore, examined whether the intestinal inflammatory process in IBS patients is the result of an altered function and/or frequency of CD25(+) Treg cells. Patients with IBS (n = 34), fulfilling the Rome II criteria, were compared with controls (n = 26). The suppressive activity of blood CD25(+) Treg cells was determined and the frequency of colonic and blood CD25(+) Treg cells was analysed by flow cytometry. The expression of the Treg marker, FOXP3 mRNA, in colonic biopsies was determined by reverse transcription-polymerase chain reaction. Blood CD25(+) Treg cells from IBS patients suppressed the proliferation of blood CD4(+)CD25(low/-) T cells. Similar frequencies of CD25(+) Treg cells were recorded in mucosa and blood of IBS patients and controls. FOXP3 mRNA was equally expressed in the colonic mucosa of patients with IBS and controls. In conclusion, the low-grade intestinal inflammation recorded in patients with IBS is not associated with an altered function or frequency of CD25(+) Treg cells.
|
|
| 7. |
- Iribarren, Cristina, 1993, et al.
(författare)
-
Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids
- 2022
-
Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map (TM) dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap ((RY)-Y-2 = 0.70, Q(2) = 0.43). Addition of fecal supernatants from healthy subjects and IBS patients (n = 9) gave rise to different gene expression profiles of the colonoid monolayers ((RY)-Y-2 = 0.79, Q(2) = 0.64). Genes (n = 22) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.
|
|
| 8. |
- Lasson, Anders, et al.
(författare)
-
Fecal Calprotectin Levels Predict the Clinical Course in Patients With New Onset of Ulcerative Colitis
- 2013
-
Ingår i: Inflammatory Bowel Diseases. - 1078-0998. ; 19:3, s. 576-581
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The clinical course of ulcerative colitis (UC) is unpredictable. During recent years, the ability of fecal biomarkers to predict relapse in inflammatory bowel disease has been evaluated. The objective of this study was to assess fecal calprotectin (FC) as a predictor of disease recurrence in patients with new onset of UC. METHODS: Sixty-nine patients were included. After the initial treatment, patients were followed up after 3 months and then yearly for 3 years. The prognostic role of FC 3 months after the initial therapy was evaluated. RESULTS: The FC levels 3 months after the diagnosis were higher in patients experiencing a relapsing disease course compared with those with a mild disease course during 1 year (median, 263; interquartile range [IQR], 100-634 μg/g versus median, 102; IQR, 38-225 μg/g; P = 0.009) and 3 years of follow-up (median, 280; IQR, 102-622 μg/g versus median, 118; IQR, 39-219 μg/g; P = 0.01). The area under the receiver operating characteristic curves using calprotectin to predict a relapsing disease course during 1 year and 3 years were 0.69 (95% confidence interval, 0.56-0.82) and 0.70 (95% confidence interval, 0.57-0.83), respectively. In the Kaplan-Meier survival analysis, a FC level >262 μg/g was associated with an increased risk of a relapsing disease course during the study period (P = 0.003). In logistic regression analysis, only FC and age were found to be independent predictors of having a relapsing disease course. CONCLUSIONS: Levels of FC 3 months after the initial therapy in patients with new onset of UC predict the disease course over the following years, and they are of value in the clinical management of these patients.
|
|
| 9. |
- Lasson, Anders, et al.
(författare)
-
Fecal calprotectin one year after ileocaecal resection for Crohn's disease - A comparison with findings at ileocolonoscopy.
- 2014
-
Ingår i: Journal of Crohn's & colitis. - : Oxford University Press (OUP). - 1876-4479 .- 1873-9946. ; 8:8, s. 789-795
-
Tidskriftsartikel (refereegranskat)abstract
- Ileocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6months prior to the ileocolonoscopy.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Maasfeh, Lujain, et al.
(författare)
-
Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission
- 2021
-
Ingår i: Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 12:4, s. 1415-1432
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. METHODS: Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. RESULTS: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4(+) T-cell activation and interferon gamma secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. CONCLUSIONS: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.
|
|
| 13. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
CD25 and TNF receptor II reflect early primary response to infliximab therapy in patients with ulcerative colitis
- 2013
-
Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 1:6, s. 467-476
-
Tidskriftsartikel (refereegranskat)abstract
- Background Although infliximab treatment is an option for patients with ulcerative colitis (UC), not all patients do respond to therapy, and cellular mechanisms leading to therapy response are incompletely known. Objective The objective of this article is to determine early effects of infliximab therapy on T cells in the blood of UC patients and if effects differed in therapy responders and nonresponders. Methods: Blood samples were obtained before and two weeks post-treatment start from 34 anti-tumor necrosis factor (TNF) therapy-naïve UC patients undergoing infliximab therapy. Response to therapy was evaluated prior to the fourth treatment dose. Expression of T cell surface markers and levels of soluble receptors and cytokines in serum were determined. Results At baseline, there were no differences in cellular, biochemical or clinical parameters between therapy responders and nonresponders. Infliximab therapy reduced frequencies of CD25+ T cells and increased frequencies of annexin V+ T cells in patients responding to infliximab, but not in nonresponding patients, two weeks after therapy start. Only therapy responders had decreased serum levels of sCD25 and sTNFRII two weeks after treatment start. In contrast, clinical parameters did not reflect therapy outcome already two weeks after therapy start. Conclusion Soluble and membrane-bound T cell receptors may be early indicators of infliximab therapy response in UC, which can be of clinical importance for the decision when to continue or to stop the treatment.
|
|
| 14. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
Cultured blood T-cell responses predict anti-TNF therapy response in patients with ulcerative colitis
- 2015
-
Ingår i: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813. ; 41:11, s. 1149-1161
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAnti-tumour necrosis factor (TNF) therapy is used for treatment of ulcerative colitis (UC). As approximately 30% of patients with UC do not benefit from the treatment, it is of clinical interest to identify biomarkers of response before therapy is initiated. AimTo identify prognostic biomarkers of anti-TNF therapy response in anti-TNF therapy-naive patients with UC. MethodsPeripheral blood cells were obtained from 56 patients with UC before therapy started. Thirty-four patients were included in an exploratory cohort and 22 patients in a validation cohort. Blood cells were stimulated in vitro with influenza vaccine with and without anti-TNF. T-cell surface receptor expression and cytokine release were determined (in total 17 variables). Treatment response was evaluated using the Mayo score 12-14weeks after the first infusion. ResultsIn the exploratory cohort, blood cells from the patients showed stronger anti-TNF-dependent suppression of T-cell surface receptor expression and cytokine secretion among therapy responders than nonresponders. In particular, anti-TNF suppressed the expression of CD25 on T cells and secretion of interleukin 5, to a higher degree in responders than in nonresponders. These variables were used to a create model to predict therapy outcome, which was confirmed in the validation cohort. Correct classification of future therapy response was achieved in 91% of the cases in the validation cohort. ConclusionThe effects of anti-TNF on cultured blood T cells, obtained before therapy started, predict treatment outcome in patients with UC.
|
|
| 15. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
Impaired Butyrate Induced Regulation of T Cell Surface Expression of CTLA-4 in Patients with Ulcerative Colitis
- 2021
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:6
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with ulcerative colitis (UC) have reduced intestinal levels of short-chain fatty acids (SCFAs), including butyrate, which are important regulators of host-microbiota crosstalk. The aim was therefore to determine effects of butyrate on blood and intestinal T cells from patients with active UC. T cells from UC patients and healthy subjects were polyclonally stimulated together with SCFAs and proliferation, activation, cytokine secretion, and surface expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) were analyzed. Butyrate induced comparable, dose dependent inhibition of activation and proliferation in blood T cells and activation in intestinal T cells from UC patients and healthy subjects. However, surface expression of the inhibitory molecule CTLA-4 on stimulated blood and intestinal T cells was impaired in UC patients and was not restored following butyrate treatment. Furthermore, unlike intestinal T cells from healthy subjects, butyrate was unable to downregulate secretion of interferon gamma (IFN gamma), interleukin (IL)-4, IL-17A, and IL-10 in UC patients. Although seemingly normal inhibitory effects on T cell activation and proliferation, butyrate has an impaired ability to reduce cytokine secretion and induce surface expression of CTLA-4 in T cells from UC patients with active disease. Overall, these observations indicate a dysfunction in butyrate induced immune regulation linked to CTLA-4 signaling in T cells from UC patients during a flare.
|
|
| 16. |
|
|
| 17. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
The Anti-inflammatory Immune Regulation Induced by Butyrate Is Impaired in Inflamed Intestinal Mucosa from Patients with Ulcerative Colitis.
- 2020
-
Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 1573-2576 .- 0360-3997. ; 43, s. 507-517
-
Tidskriftsartikel (refereegranskat)abstract
- Altered gut microbiota composition and reduced levels of short-chain fatty acids, such as butyrate, have been identified as key components of ulcerative colitis (UC). We aimed to determine and compare effects of butyrate on the intestinal immune profile of UC patients with active disease and non-inflamed controls. Biopsies were cultivated during 6 h with or without butyrate. Cytokines were measured in supernatants and mRNA gene expression was analyzed in biopsies using Qiagen RT2 Profiler PCR Arrays. The intestinal immune profile of cultured biopsies, as determined by mRNA gene expression and secreted cytokines, differed between inflamed UC samples and controls. Principal component analysis revealed that addition of butyrate differently regulated mRNA expression in inflamed biopsies from UC and non-inflamed biopsies from controls. Highly discriminant and predictive orthogonal partial least squares discriminant analyses identified 29 genes for UC (R2 = 0.94, Q2 = 0.86) and 23 genes for controls (R2 = 0.90, Q2 = 0.71) that were most regulated by butyrate. UC displayed more up-regulation of genes as compared with controls, and controls displayed the most prominent down-regulations. Ingenuity Pathway Analysis identified a down regulation of the Neuroinflammation Signaling pathway and predicted inhibition of the categories Inflammatory response, cellular movement, and cellular development as top diseases and functions, respectively, for controls but not for UC. In conclusion, butyrate has a different effect on gene regulation and more potently down-regulates gene expression of inflammatory pathways in non-inflamed controls than in inflamed tissue of UC patients. These discrepancies may at least partly explain why anticipated anti-inflammatory effects of local butyrate induction or supplementation are not always obtained.
|
|
| 18. |
- Magnusson, Maria K, 1972, et al.
(författare)
-
The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis
- 2017
-
Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 23:6, s. 956-966
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. Methods: Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT2 Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). Results: At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R-2 = 0.395, P < 0.0001). Conclusions: In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.
|
|
| 19. |
- Mavroudis, Georgios, et al.
(författare)
-
Mucosal and Systemic Immune Profiles Differ During Early and Late Phases of the Disease in Patients With Active Ulcerative Colitis
- 2019
-
Ingår i: Journal of Crohns & Colitis. - : Oxford University Press (OUP). - 1873-9946. ; 13:11, s. 1450-1458
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Alterations in the immunopathogenesis in ulcerative colitis [UC] during the disease course have been proposed. We therefore aimed to determine mucosal and systemic immune profiles in individual patients at the time of diagnosis [early disease] and after 10 years [late disease]. Methods: Patients with UC provided serum and mucosal biopsies during a flare in early and in late disease. Serum samples were analysed using the Olink Proseek Inflammation panel. mRNA gene expression of biopsies was analysed using the Qiagen RT2 Profiler PCR Arrays Antibacterial response and T Helper Cell Differentiation. Results: Orthogonal projections to latent structures discriminant analyses [OPLS-DA] demonstrated that the profile of 15 serum proteins discriminated in early and late disease [R2 = 0.84, Q2 = 0.65] in 15 UC patients. Eight of these proteins were differently expressed between the groups [Q <0.05]. Further, OPLS-DA of the mRNA profiles in biopsies strongly discriminated early and late disease with high predictability [R2 = 0.96, Q2 = 0.89]; 42 genes were differently expressed at the two time points [Q <0.05]. Finally, principal component analysis showed that T helper [Th] 1- and Th2-related genes were associated with early disease and late disease, respectively, and hierarchical cluster analysis was able to cluster patients with early from late disease with only minor overlap. Conclusions: Mucosal and systemic immune profiles differ between early and late disease in patients with active UC, with a transition from a Th1- to a Th2-driven disease in the intestine. Improved understanding of the variation in immunopathogenesis during the disease course in UC is important to guide individualised treatment decision making.
|
|
| 20. |
|
|
| 21. |
- Öhman, Lena, 1967, et al.
(författare)
-
A controlled study of colonic immune activity and beta7+ blood T lymphocytes in patients with irritable bowel syndrome.
- 2005
-
Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - 1542-3565. ; 3:10, s. 980-6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The mechanisms behind irritable bowel syndrome (IBS) are incompletely understood. Recently several studies have suggested a low-grade colonic inflammation as initiator of the gut dysfunctions recorded in this patient group. The aim of this study was to characterize the phenotype and homing properties of colonic and peripheral blood lymphocytes in patients with IBS. METHODS: Patients with IBS (n=33), defined by the Rome II criteria, were compared with UC patients (n=23) and control subjects (n=15) without gastrointestinal symptoms. Colonic and peripheral blood lymphocytes were analyzed by flow cytometry. Secretion of IFN-gamma from intestinal biopsies was determined by enzyme-linked immunosorbent assay, and immunohistochemical staining of colonic biopsies was performed. RESULTS: IBS patients displayed an increased frequency of peripheral blood CD4+ and CD8+ T cells expressing the gut homing integrin beta7. Accordingly, IBS and UC patients had an augmented frequency of lamina propria CD8+ T cells in the ascending colon as compared with control subjects. The frequency of intestinal T cells expressing integrin beta7+ was unaltered in IBS and UC patients, although the expression of mucosal addressin cell adhesion molecule-1+ endothelium, the ligand for integrin beta7, was increased in the ascending colon of IBS and UC patients as compared with control subjects. CONCLUSIONS: Patients with IBS exhibit an enhanced immune activity in the gut and an increased frequency of integrin beta7+ T lymphocytes in the peripheral blood. Our data further support the hypothesis of IBS being at least partially an inflammatory disorder.
|
|
| 22. |
- Öhman, Lena, 1967, et al.
(författare)
-
Altered levels of fecal chromogranins and secretogranins in IBS: relevance for pathophysiology and symptoms?
- 2012
-
Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 107:3, s. 440-7
-
Tidskriftsartikel (refereegranskat)abstract
- Chromogranins (Cg) and secretogranins (Sg) are proteins ubiquitous in secretory cells of the enteric, endocrine, and immune systems, and may reflect activity of these systems. We therefore performed a hypothesis generating study to evaluate the association between fecal levels of CgA, CgB, SgII, and SgIII, with the clinical and pathophysiological phenotype of irritable bowel syndrome (IBS) patients.
|
|
| 23. |
- Öhman, Lena, 1967, et al.
(författare)
-
B-cell activation in patients with irritable bowel syndrome (IBS).
- 2009
-
Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 21:6
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probiotic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19(+) B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells.
|
|
| 24. |
- Öhman, Lena, 1967, et al.
(författare)
-
Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2-6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3-10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting >= 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.
|
|
| 25. |
- Öhman, Lena, 1967, et al.
(författare)
-
Increased TLR2 expression on blood monocytes in irritable bowel syndrome patients.
- 2012
-
Ingår i: European journal of gastroenterology & hepatology. - 1473-5687. ; 24:4, s. 398-405
-
Tidskriftsartikel (refereegranskat)abstract
- The understanding of the mechanisms for increased immune activation in subgroups of patients with irritable bowel syndrome (IBS) is incomplete. We hypothesized that monocytes are more activated in patients with IBS than in the healthy population. We therefore examined activation phenotype and cytokine secretion of blood monocytes.
|
|
| 26. |
- Öhman, Lena, 1967, et al.
(författare)
-
T-cell activation in patients with irritable bowel syndrome.
- 2009
-
Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 104:5, s. 1205-12
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients. METHODS: Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed. RESULTS: IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity. CONCLUSIONS: IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.
|
|
