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- Lettesjö, Helene, et al.
(författare)
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Enhanced interleukin-18 levels in the peripheral blood of children with coeliac disease
- 2005
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 139:1, s. 138-143
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Tidskriftsartikel (refereegranskat)abstract
- Coeliac disease (CoD) is a small intestinal disorder characterized by villous atrophy, crypt cell hyperplasia and an increased production of T helper cell type 1 (Th1) cytokines. Interleukin (IL)-18 is a pro-inflammatory cytokine that has a crucial role in maintaining the Th1 response. In this study, the serum levels of IL-18 were measured in children with CoD or other gastrointestinal diseases in order to evaluate the possibility of using IL-18 as a disease activity marker. IL-18 levels were higher in samples from CoD patients [median 443 pg/ml (148-885)] compared to healthy controls [median 205 pg/ml (11-379)], P <0.05. In contrast, the levels of IL-18 were not enhanced significantly in the serum from patients with inflammatory bowel disease (IBD) [median 324 pg/ml (207-546)] or in the disease control group [median 303 pg/ml (2-689)]. In CoD patients, after 2 weeks of gluten challenge (GC), serum IL-18 was unchanged [median 268 pg/ml (59-458)] compared to patients on a gluten-free diet [median 220 pg/ml (53-600)], while IL-18 was increased after 12 weeks of GC [median 551 pg/ml (94-952)], P <0.01. The IL-18 levels correlated with IgA anti-transglutaminase antibody levels (rs=0.59, P=0.016) in serum from untreated CoD patients, and IL-18 also followed the degree of small intestinal villous atrophy in 12 out of 19 CoD patients. Our results support the view that serum IL-18 concentrations in children with CoD follow disease activity, suggesting a role for IL-18 in the induction of an inflammatory Th1-response after gluten exposure.
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- Högberg, Lotta
(författare)
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Childhood coeliac disease : clinical aspects of heredity, diagnosis and dietary therapy
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Childhood coeliac disease (CD) is defined as a lifelong disorder, in which the small bowel mucosa is abnormal as a result of exposure to gluten in the diet. The mucosal damage improves on treatment with a gluten-free diet, but recurs within two years of reintroduction of gluten. If there is no mucosal relapse within two years of gluten challenge the condition is called transient gluten intolerance. We describe a case of CD, in whom small bowel biopsy performed yearly demonstrated that mucosal relapse took 14 years of gluten challenge. This is an exceptionally long time questioning the existence of the condition transient gluten intolerance.Small bowel biopsy is the golden standard in diagnosing CD but an uncomfortable investigation in a child. An effective sedation of the child is necessary. In a randomised study of intranasal versus intravenous midazolam as sedation of children undergoing small bowel biopsy we showed that both administration routes are effective and safe. Intranasal midazolam produced nasal discomfort. Thus, the intravenous route of administration is to be preferred.In a previous study at our clinic 20-25 years ago all first-degree relatives (n=100) of 32 index patients with CD were investigated with small bowel biopsy. Two cases of CD were found. In the present reinvestigation of the relatives (n=120) using serological screening, 8 new cases of CD were found. The overall prevalence of CD in the first-degree relatives is 8.3%. Six of the new cases were children of the index patients. The remaining 2 newly diagnosed cases had had some enteropathy, not classified as CD, in the previous study. This is the first study of first-degree relatives of coeliacs followed for as long as 20-25 years. The study shows that there is a strong genetic component in the aetiopathogenesis of CD.The compliance to gluten-free diet, among 29 adult coeliacs, who had been diagnosed in childhood (one group before and one group after 4 years of age) was assessed by dietmy questionnaire and serological markers. The compliance was 80% in the patients diagnosed before 4 years and 36% in those diagnosed later in childhood. This significant difference indicates that a diagnosis in early childhood makes it easier for a coeliac patient to keep to a strict gluten-free diet. This is a clinically important observation.In a double-blind randomised multi-centre study of oats in the gluten-free diet during a study period of one year, children with CD were carefully monitored using small bowel biopsy and serological markers. The results indicate that oats are tolerated by coeliac children. This is important, since additional oats improve the palatability and fibre content of the fairly low-fibre standard glutenfree diet. This makes it easier for a patient with CD to adhere to the gluten-free diet, which is very important in order to minimise the risk for potential complications.
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- Paul-Visse, Gesine, et al.
(författare)
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The adult human brain harbors multipotent perivascular mesenchymal stem cells.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain.
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