Zöliakie ist durch eine dysregulierte Immunreaktion auf die in Getreiden enthaltene Proteinfraktion Gluten charakterisiert. Die Assoziation der Erkrankung mit Polymorphismen in immunregulatorischen Genen weist auf eine Rolle von regulatorischen T-Zellen im Krankheitsgeschehen hin. Foxp3+ regulatorische T-Zellen haben eine essentielle Bedeutung für die Aufrechterhaltung der intestinalen Immunhomöostase und die Limitierung von Autoimmunität. In der vorliegenden Arbeit wurde eine 2005 bis 2010 diagnostizierte Gruppe von 51 Kindern und Jugendlichen mit Zöliakie untersucht. Diese Gruppe wurde mit 51 geschlechts- und altersadaptierten Kontrollen ohne Zöliakie verglichen. Es wurden anamnestische, paraklinische und histologische Daten mit der Verteilung von CD3+Foxp3+ regulatorischen T-Zellen in der Dünndarmschleimhaut untersucht. Patienten mit Zöliakie wiesen eine leichte Anämie, jedoch keine signifikante Wachstums- und Gewichtsentwicklung auf, was die oligosymptomatische Verlaufsform in der Gesamtkohorte unterstreicht. Es konnte gezeigt werden, dass CD3+Foxp3+ regulatorische T-Zellen bei Zöliakie-Patienten vermehrt in der Dünndarmschleimhaut akkumulieren. Weiterhin korreliert die Häufigkeit CD3+Foxp3+ regulatorischer T-Zellen sowohl mit dem Schweregrad der Schleimhaut-schädigung (gemessen an der Marsh-Oberhuber-Klassifikation, dem Zotten-Krypten Verhältnis oder der Zahl der intraepithelialen Lymphozyten) als auch mit den Titern Zöliakie-spezifischer Antikörper. Die Akkumulation CD3+Foxp3+ regulatorischer T Zellen lässt sich partiell als Folge einer Anreicherung von CD4+ T-Zellen auf Kosten CD8+ T-Zellen erklären. Die Daten weisen darauf hin, dass Foxp3+ regulatorische T Zellen sekundär als Folge des gluteninduzierten Entzündungsprozesses in der Schleimhaut akkumulieren, diesen offensichtlich aber nicht effektiv begrenzen. Die mögliche Assoziation der Immundysregulation der Zöliakie mit Foxp3+ regulatorischen T-Zellen ist damit nicht durch eine numerische Reduktion sondern wahrscheinlich durch partielle funktionelle Defekte bedingt.:Bibliographische Beschreibung 2 Inhaltsverzeichnis 3 Abkürzungsverzeichnis 5 1. Einleitung 6 1.1 Zöliakie 6 1.1.1 Epidemiologie 6 1.1.2 Äthiopathogenese 6 1.1.3 Diagnostik 10 1.1.4 Therapie 11 1.2 Regulatorische T-Zellen 12 1.2.1 Typen regulatorischer T-Zellen 13 1.2.2 Suppressionsmechanismen von CD4+CD25+Foxp3+ regulatorischen T-Zellen 14 1.3 Zielstellung der Arbeit 17 2. Material und Methoden 19 2.1 Ethikvotum 19 2.2 Ablauf der Studie 19 2.3 Rekrutierung der Studienpopulation 20 2.3.1 Gruppe der Zöliakie-Patienten 22 2.3.2 Kontrollgruppe 22 2.4 Telefoninterview – Erfassung anamnestischer Daten 23 2.5 Anthropometrische Daten 23 2.6 Klinische Chemie 24 2.7 Zöliakie - spezifische Antikörper 24 2.8 Färbungen der histologischen Schnitte 25 2.8.1 Vorbereitung der Gewebeproben 25 2.8.2 Hämatoxylin-Eosin (HE)-Färbung 25 2.8.3 Immunhistochemische Färbungen 26 2.8.4 Immunfluoreszenzfärbungen 27 2.8.5 Mikroskopie und Fotographie 28 2.9 Morphometrische Messung der histologischen Schnitte 28 2.9.1 Zotten- und Kryptenmessung 28 2.9.2 Bestimmung der Anzahl intraepithelialer Lymphozyten 29 2.9.3 Ermittlung von Zelldichten 29 2.10 Statistische Auswertung 30 3. Ergebnisse 31 3.1 Charakterisierung der Studienpopulation 31 3.1.1 Der Schweregrad der Schleimhautschädigung korreliert mit dem Geschlecht 31 3.1.2 Die Einführung glutenhaltiger Nahrung erfolgt bei Kindern mit Zöliakie früher 32 3.1.3 Keine Unterschiede in Körpergröße und Körpergewicht zwischen den Studiengruppen 36 3.1.4 Klinische Chemie - Leichte Anämie bei Kindern und Jugendlichen mit Zöliakie 39 3.1.5 Serologische Charakterisierung der Studienpopulation 41 3.2 Histologische Charakterisierung der Dünndarmschleimhaut 42 3.2.1 Das Zotten-Kryptenverhältnis sinkt mit zunehmendem Marsh-Stadium 42 3.2.2 Zunahme von intraepithelialen Lymphozyten bei Patienten mit Zöliakie 44 3.2.3 Erhöhte Infiltrationsdichte in der Lamina propria von Zöliakie-Patienten 46 3.3 Die Anzahl von CD3+Foxp3+ T-Zellen ist in der Dünndarmschleimhaut von Zöliakie- Patienten erhöht 48 3.4. Erhöhte CD4/CD8-Ratio in der Dünndarmschleimhaut von Zöliakie-Patienten 50 3.5 Dichte von regulatorischen Foxp3+ T-Zellen korreliert mit histologischen, hämatologischen und serologischen Parametern 52 4. Diskussion 56 4.1 Zöliakie – Umweltfaktoren und Immunregulation 56 4.2 Rolle von Foxp3+ T-Zellen bei Zöliakie 58 4.3 Immungenetik bei Zöliakie 63 4.4 Stärken und Schwächen der Studie 68 5. Zusammenfassung 69 Literaturverzeichnis 71 Appendix 84 Lebenslauf 85 Persönliche Daten 85 Danksagung 86 Erklärung über die eigenständige Abfassung der Arbeit 88

Celiac disease is a common autoimmune disease triggered by gluten-containing foods (wheat, barley and rye) in genetically predisposed individuals. We present a patient with celiac disease complicated by severe aphthous stomatitis resulting in impairing swallowing, chewing and speaking. This led to weight loss, psychosocial problems as well as inability to perform her work. A variety of topical and systemic medications used resulted in either no improvement or only partial alleviation of the patient's symptoms. After informed consent, etanercept was initiated and resulted in complete remission of aphthous stomatitis, decrease in arthralgia and fatigue and considerable improvement in her quality of life. The use of newer biological agents for selected and severe manifestations of celiac disease may lead to improved morbidity in these patients, but more studies are needed to determine long-term efficacy as well as safety of these drugs in the mucosal and/or systemic complications of this disease.

Celiac disease is a common autoimmune disease triggered by gluten-containing foods (wheat, barley and rye) in genetically predisposed individuals. We present a patient with celiac disease complicated by severe aphthous stomatitis resulting in impairing swallowing, chewing and speaking. This led to weight loss, psychosocial problems as well as inability to perform her work. A variety of topical and systemic medications used resulted in either no improvement or only partial alleviation of the patient's symptoms. After informed consent, etanercept was initiated and resulted in complete remission of aphthous stomatitis, decrease in arthralgia and fatigue and considerable improvement in her quality of life. The use of newer biological agents for selected and severe manifestations of celiac disease may lead to improved morbidity in these patients, but more studies are needed to determine long-term efficacy as well as safety of these drugs in the mucosal and/or systemic complications of this disease.

Bakgrund: Celiaki är en autoimmun sjukdom som påverkar två delar av tunntarmen. En autoimmun reaktion påbörjas vid intag av gluten (gliadin) som främst finns i sädesslagen vete, korn och råg. De sociala situationer som personer med Celiaki upplever är komplexa. Sjuksköterskans stöd till personer med Celiaki är viktigt för att bidra till en ökad livskvalité och kan även stödja till att bibehålla, främja och återfå hälsa. Syfte: Var att belysa personer med Celiakis behov av stöd ur ett omvårdnadsperspektiv. Metod: Studien genomfördes som en allmän litteratur studie och åtta resultatartiklar framkom. Resultatartiklarna granskades, bearbetades och sammanställdes till tre teman. Resultat: De teman som framkom var: Sjuksköterskans stöd- Att vara en del av ett sammanhang, Sjuksköterskans roll- Att dela erfarenheter, Sjuksköterskans betydelse- Att ge stöd för personer med Celiaki. Det framkom från resultatet att personer med Celiaki påverkades både psykiskt och socialt och därmed i behov av stöd. Konklusion: Från resultatet framkom det att personer med Celiaki är i behov av stöd. En okunskap om sjukdomen från allmänheten påverkar personer med Celiaki i sociala sammahang. / Background: Celiac disease is an autoimmune disease that affects two parts of the small intestine. An autoimmune reaction is initiated by consuming gluten (gliadin) which is mainly found in wheat, barley and rye. The social situation that people with Celiac disease experience is complex. The nurse's support for people with Celiac disease is important to contribute to an increased quality of life and can also help maintain, promote and regain health. Purpose: To highlight people with Celiac disease's need for support from a nursing perspective. Method: The study is conducted as a general literature study and eight result articles appeared. The eight results articles was reviewed, processed and compiled into three themes. Results: The themes that emerged was: The nurse's support- To be part of a context, The nurse's role- To share experiences, The nurse's importance of providing support for people with Celiac disease. It emerged from the results that people with Celiac disease were affected both mentally and socially and thus are in need of support. Conclusion: The results showed that people with Celiac disease are in need of support. The lack of knowledge by the general public of the disease affects people with Celiac disease in the social context

Celiac disease (CD) is a highly prevalent autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+ T cell activation culminates in intraepithelial T cell (T-IEL) mediated intestinal damage remain unclear. Here, we performed multiplexed-single cell analysis of intestinal and gluten-induced peripheral blood T cells from patients with different celiac disease states and controls. Untreated, active CD (ACD) and potential CD (PCD) were associated with an enrichment of activated intestinal T cell populations including CD4+ follicular T-helper (TFH) cells, regulatory T cells (Tregs), and Natural CD8+ αβ and γδ T-IELs. Natural CD8+ αβ and γδ T-IELs expressing activating Natural Killer Cell Receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet (GFD) without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. Following gluten ingestion, both αβ and γδ T cell clones from this memory population of T-IELs circulated systemically with gluten-specific CD4+ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. In patient-derived organoid (PDO) model of CD, gluten exposure induced the presence of this cytotoxic, NKR-expressing population exclusively in PDOs generated from CD patients. The increased abundance of cytotoxic, NKR-expressing T-IELs following gluten exposure corresponded to histologic observations of altered organoid morphology including degenerated organoid structures and the presence of infiltrating immune cells co-localized with apoptotic epithelial cells. Collectively, these findings suggest that these cytotoxic, NKR-expressing T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+ T cells following gluten ingestion to mediate the destruction of intestinal epithelial cells in CD.

The purpose of this qualitative descriptive study was to examine parental experiences and challenges raising children with both T1DM and CD. Twenty-six families, including 30 parents (25 mothers, 4 fathers, and one custodial grandmother), participated in a 30-60 minute audio-recorded interview designed to explore parental experiences raising children with both T1DM and CD. Participants were asked IRB approved open-ended questions about their experiences raising a child with both diseases. Direct quotations best representing categories/sub-categories were identified through selective coding. Analysis revealed seven main themes: Six themes parents are concerned about, including (a) their child's health complications, b) the challenges of daily disease management, c) the time, resources, and expense required to manage both diseases, d) their child's emotional/mental health, e) support from healthcare providers, f) community support/understanding, and lastly (observed by the researcher) g) how positive versus negative experiences and adaptation influence the way parents and children meet their challenges and perceive the future. Parents raising children with both T1DM and CD face many daily challenges as they learn to manage both lifelong chronic diseases. They need access to and support from healthcare providers for up-to-date education, treatment options, and community resources. Positive provider relationships were identified as: being responsive to parent's questions, willing to listen to parents, creating an open and honest dialogue with parents, having a personal relationship with the child, and being a patient advocate. Future research should examine broader ethnic and socioeconomic populations. A quantitative study design could also be used to assess the level of caregiver burden, in order to compare different ethnic and socioeconomic groups.

No description available.

No description available.

<p>Abstract Redacted.</p> / Master of Science (MSc)

Background: Nutritional deficiencies are frequent in celiac disease (CeD), and one of the most common is zinc (Zn) deficiency. Supplements are often prescribed to treat Zn deficiency; however, they have been associated with adverse events and reduced absorption of other minerals. Data collected in our clinic showed that 38% of CeD patients would opt for a diet to improve Zn, however, such a diet may be challenging due to food interactions with phytic acid, which blocks Zn absorption. Therefore, the feasibility and efficacy of a Zn-optimized diet compared to supplementation is unknown. Aims: To assess the feasibility of the protocol and collect data on estimated effect sizes for secondary outcomes to plan a properly powered randomized controlled trial (RCT). Methods: We conducted an open-label, pilot RCT. CeD patients were randomized to Zn supplementation (Zn gluconate 25mg) or a Zn-optimized diet for 3 months and followed up with a 3-month pragmatic approach. We evaluated enrollment rates and adherence to both interventions. Plasma and urine Zn, stool samples, and questionnaires were collected pre- and post-intervention. Results: We enrolled 28 participants and 16 of them have completed the study. Interim analysis shows an enrollment fraction of 26% (i.e. 28/108 eligible participants), and a dropout rate of 17.9%. Eighty-two % of participants allocated to the Zn-supplement intervention and 50% in the dietary intervention were compliant at 3 months. Based on the effect size for normalization of plasma Zn at 3 months, 142 participants are required for an adequately powered RCT in the future. There were no significant differences in gastrointestinal or extra-intestinal symptoms, quality of life, anxiety and depression or adverse events between interventions. Conclusion: Based on this preliminary analysis, recruitment of participants will take 6 months longer than expected. Assessment of reasons for diet non-adherence will allow implementation of strategies to improve feasibility. / Thesis / Master of Science in Medical Sciences (MSMS)