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- Kumawat, Ashok Kumar, 1982-
(författare)
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Adaptive immune response in the intestinal mucosa of microscopic colitis patients
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microscopic colitis (MC) is a chronic diarrhoeal disease of unknown aetiology, comprising collagenous colitis (CC) and lymphocytic colitis (LC). The nature of the adaptive local immune responses in the mucosa of MC patients is however far from elucidated. The present study investigates phenotypic and functional characteristics of the adaptive local immune responses in the colonic mucosa of these patients.Our immunohistochemistry and flow cytometry studies (Paper I & II) demonstrated increased frequencies of CD8+ T cells in the colonic epithelium and lamina propria of both LC and CC patients compared to controls, whereas the frequencies of CD4+ T cells were unaltered or reduced. Our flow cytometry data revealed increased local activation of both CD4+ and CD8+ T cells in the lamina propria as well as the intraepithelial compartment of CC and LC patients compared to controls, demonstrated as increased proportions of these cells expressing the active/memory marker CD45RO and the proliferation marker Ki67.Analysis of recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients revealed reduced TRECs levels in these patients compared to controls (Paper III). These results suggests that the observed increased numbers of T cells in the mucosa of CC and LC patients is due to the expansion of local resident T cells rather than direct recruitment of recent thymic emigrants to the mucosa.Molecular analysis of T helper (Th) cell and cytotoxic T lymphocyte (Tc) mucosal cytokines at messenger and protein levels in the colonic biopsies from CC and LC patients demonstrated a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile and revealed significant differences in the mucosal cytokine levels in CC and LC patients compared to controls (Paper IV).Finally, we have set up an in vitro model to investigate how the colonic milieu affects the activation and differentiation of T lymphocytes (Paper V). Our preliminary data indicate increased production of both pro inflammatory and antiinflammatory cytokines by peripheral blood T cells in the presence of soluble factors from the inflamed colonic mucosa of CC patients compared to controls.
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| 2. |
- Wickbom, Anna, 1970-
(författare)
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Epidemiological aspects of microscopic colitis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microscopic colitis (MC) constitutes the main entities collagenous colitis (CC) and lymphocytic colitis (LC), diseases that are relatively recently described (in 1976 and 1989, respectively).The aims of this thesis were to study the epidemiology of MC, to describe how these diseases affect patients in terms of symptom burden and health-related quality of life (HRQoL), to study potential risk factors such as familial factors, childhood circumstances, educational level, marital status, smoking and comorbidity, and to describe a cohort of patients with ulcerative colitis (UC) or Crohn’s disease (CD) and subsequent MC, and vice versa.During 1999–2008 in Sweden, the mean annual incidence of MC was 10.2 per 105 inhabitants, compared with 5.2 per 105 inhabitants for CC, and 5.0 per 105 inhabitants for LC. The prevalence of MC on 31 December 2008 was 123 per 105 inhabitants. Women appeared to be especially affected – the female:male ratio was 3.6:1 in CC and 4.6:1 in LC.Patients’ HRQoL is impaired both in active CC and in LC. Patients with CC in clinical remission have persisting symptoms: abdominal pain, fatigue, arthralgia and myalgia; LC patients in remission have persistent fatigue compared with controls. This illustrates that the longterm outcome is different in CC compared with LC.Microscopic colitis is associated with a family history of MC, indicating that familial factors may play a role in the pathogenesis of this disease. We confirm earlier reports that smoking is a risk factor in MC.In the present study population, CC was associated with rheumatic disease and previous appendicectomy. Moreover, CC and LC were associated with thyroid disease and coeliac disease and, interestingly, with a history of UC.Most patients with UC or CD and subsequent MC, or vice versa, had UC or CD first and later developed MC. The majority had extensive UC and later onset of CC. Microscopic colitis should be considered in patients with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of mucosal inflammation.
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| 3. |
- Stenberg, Reidun, 1954-
(författare)
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Dietary antibodies and gluten related seromarkers in children and young adults with cerebral palsy
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background & Aims: Cerebral palsy (CP), the most common physical disorder in children that affect motor function, is associated with a low weight and height. Celiac disease (CD), an autoimmune disorder precipitated by ingestion of gluten, is another common chronic disease in children that has a negative impact on growth. Based on our findings in a small pilot study, antibodies against gluten, dietary antigens and antibodies against transglutaminase 6(TG6) a new possible gluten related neurological marker have been investigated in an extended group of children with CP. The main aim of this thesis was to find out if the children with elevated gluten related antibodies have enteropathy consistent with CD and if they have antibodies to other dietary antigens as well. We further wanted to study if elevated levels of antibodies were associated to their weight, subtypes of CP and also to investigate if there were an association between the brain damage seen in CP and antibodies against TG6.Methods: Ninety nine children with CP and matched (study4) controls (study3) were analysed for antibodies against gluten, TG6, egg white, lacto-globulin, casein and wheat. Small bowel biopsies were analysed in the majority of the children with antibody positivity, both by routine procedures and by extended analyse (study 2).Results: Significantly elevated levels of gluten related seromarkers and antibodies against casein, lacto globulin and egg white were found in the CP-group compared to matched controls. The overall elevated levels of antibodies were more frequent in the tetraplegic (TP) and dyskinetic (DK) CP -subtypes having the most severe neurologic handicap and undernourishment. Routine and extended small bowel biopsies analysis did not indicate an increased prevalence of CD. Elevated antibodies against TG6 were found in the CP-group and significantly in the tetraplegic CP-subgroup.Conclusion: Children with CP do not have increased prevalence of celiac disease but have elevated levels of gluten related seromarkers as well as antibodies against other dietary proteins compared to matched controls. There was a correlation between underweight, CP-subtypes (TP/DK) and occurrence of the tested antibodies suggesting disturbed intestinal permeability related to underweight. Compared to controls TG6 autoantibodies were found in the TP-subtype of CP that could be a result due to the brain damage.
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