| 1. |
- Grännö, O., et al.
(författare)
-
Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
- 2024
-
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I660-I661
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).
|
|
| 2. |
- Hallert, C, et al.
(författare)
-
Living with coeliac disease.
- 2002
-
Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521 .- 1502-7708. ; 37, s. 39-42
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Järnerot, G, et al.
(författare)
-
Familial occurrence of microscopic colitis: a report on five families
- 2001
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 36:9, s. 959-962
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Gustavsson, Anders, et al.
(författare)
-
Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
-
Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
-
Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
|
|
| 8. |
|
|
| 9. |
- Myrelid, Pär, 1970-, et al.
(författare)
-
Atopic manifestations are more common in patients with Crohn disease than in the general population
- 2004
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 39:8, s. 731-736
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The role of TNF-α in Crohn disease is now well established and anti-TNF-α is frequently used as a second- or third-line treatment. Tumor necrosis factor-α (TNF-α) is traditionally associated with macrophages but has recently also been found in mast cells of the ileal wall in patients with Crohn disease. As it is well known that mast cells and TNF-α play important roles in atopic manifestations like asthma, allergic rhinitis, and eczema the aim of this study was to investigate whether these are seen more commonly in Crohn patients than in the general population. Methods: Patients with Crohn disease (n = 308), aged 18-50 years, living in the Linköping region in southeast Sweden, were asked to answer a questionnaire regarding the presence of any kind of atopic manifestations. The questionnaire was also sent to 930 controls collected from the Southeastern Region Population Registry. The controls were matched according to age, sex, and place of residence. Results: The response rate among the Crohn patients was 91% (280/308) and among controls 84% (779/930). Eczema was a significantly more frequent manifestation, being almost twice as common in Crohn patients (27%) as in the general population (16%). Adjustment by logistic regression for place of residence, gender, age and coexistence of any other atopic manifestation did not change the odds ratios significantly. Conclusion: Atopic manifestations as a group, and eczema as a single manifestation, are significantly more frequent in Crohn patients than in the general population.
|
|
| 10. |
|
|
