Tyrimo objektas. Celiakija yra labai dažna virškinimo trakto liga. Jos paplitimas Europoje ir Šiaurės Amerikoje 1 iš 100-300 suaugusių ir vaikų. Lietuvoje duomenų apie celiakijos paplitimą nėra, ši liga diagnozuojama tik pavieniais atvejais [29]. Sergantieji imumoglobulino A (IgA) deficitu 10 kartų dažniau serga celiakija negu sveikieji. Viršutinių kvėpavimo takų ir virškinimo trakto infekcijos, autoimuninės ligos ir onkologiniai susirgimai taip pat dažnesni sergantiesiems IgA deficitu [143, 163-168]. Lietuvoje duomenų apie IgA deficito paplitimą nėra [29]. Darbo tikslas. Nustatyti Vilniaus miesto 11-13 m. vaikų celiakijos ir IgA deficito paplitimą. Tyrimo medžiaga ir metodai. Gavus Lietuvos bioetikos komiteto leidimą nuo 2009 metų sausio mėnesio iki 2010 metų kovo mėnesio ištirta 1000 vaikų nuo 11 iki 13 metų amžiaus, kurie mokėsi šešiose lietuviškose Vilniaus miesto mokyklose. Mokyklos pasirinktos atsitiktiniu atrankos būdu. Jose buvo išdalintos asmens informavimo formos (tėvams priedas nr. 1 ir vaikams priedas nr. 2), kuriose buvo aprašytas biomedicininis tyrimas, jo eiga ir nauda. Vaikams, kurių tėvai sutiko atlikti celiakijos tyrimą, buvo nustatomi audinių transgliutaminazės IgA klasės (aTG IgA) antikūnai ir bendras IgA kiekis kapiliarinio kraujo laše. Tyrimo metu buvo naudojami Biocard TM celiakijos testai (Ani Biotech OY, Suomija). Tyrimo atsakymas buvo gaunamas ir įvertinamas po 5 min. Nustačius aTG IgA klasės antikūnus, vaikai buvo nukreipti į Vilniaus universitetinę... [toliau žr. visą tekstą] / Object. Coeliac disease is one of the most prevalent gastrointestinal disorder. It‘s prevalence in Europe and North America is 1 of 150-300 adults and children. In Lithuania there are no data on prevalence of coeliac disease but it‘s seems that there is hypodiagnosis [29]. IgA-deficient individuals have a tenfold risk for coeliac disease compared with the general population. Patients with IgA deficiency have a tendency to develop recurrent sinopulmonary and gastrointestinal infections, allergies, autoimmune diseases and malignancies [148-154]. There are no data on the prevalence of IgA deficiency in Lithuania [29]. The aim. To determine the prevalence of coeliac disease and IgA deficiency among 11-13 years children in Vilnius. Material and methods. From January 2009 to March 2010 we investigated 1000 children (11-13 years of age) for coeliac disease and immunoglobulin A (IgA) deficiency from six Vilnius secondary schools. We examined capillary blood for tissue transglutaminase IgA class antibodies (tTG IgA) and total IgA with Biocard TM test (Ani Biotech OY, Finland) for children whose parents agreed to do this test. The results were evaluated after 5 min. Children with positive test results (tTG IgA positive or total IgA deficiency) underwent small bowel endoscopy with biopsies at Vilnius University Children Hospital to confirm or deny the diagnosis of coeliac disease. We get permission for this study from Lithuanian Bioethics Committee. Results. Two of 1000 children were... [to full text]

Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) and coeliac disease are debilitating gastrointestinal diseases that seriously affect the quality of life of those affected. Under normal circumstances, the intestinal immune system is maintained in a state of controlled inflammation, whereby balance exists between protective immunity, mediated by effector cells, and tolerance mediated by cells with regulatory function. However, an aberrant immune response is believed to contribute to the intestinal inflammation present in individuals afflicted by these diseases. This thesis investigated the involvement of CD4⁺ CD25[superscript]high Foxp3⁺ Regulatory T cells (Treg) and Th17 Effector cells in both inflammatory bowel disease (IBD) and coeliac disease. The reciprocal relationship between Treg and Th17 cells under certain cytokine conditions, has prompted the exploration of these two cell types in IBD and coeliac disease. Previous studies have examined these factors individually in a range of diseases, however, to our knowledge the study of both Treg and Th17 in IBD and coeliac disease subjects represents a novel area of research. Crohn’s disease (CD), ulcerative colitis (UC) and coeliac disease subjects were recruited through the Department of Gastroenterology and Hepatology at The Queen Elizabeth Hospital (QEH) in Adelaide, South Australia. In total, one-hundred and seventeen subjects were enlisted in this study to donate blood samples. In addtion, intestinal biopsy samples were collected from fifty-six subjects undergoing colonoscopy at the QEH Department of Gastroenterology and Hepatology. All subjects participated, with informed consent and ethics approval. Treg and Th17 cell numbers were investigated in the peripheral blood of Crohn’s disease, ulcerative colitis, coeliac disease and control subjects using multi-colour, intracellular flow cytometry. A decrease in Treg cell numbers and an increase in Th17 cell numbers was observed in IBD, but not in coeliac disease. Closer investigation into the ratio of Treg and Th17 cells within patients identified a near 1:1 Treg/Th17 ratio in control subjects, but a lower Treg/Th17 ratio in IBD patients. This suggested a disturbance in regulatory and effector cell equilibrium. Furthermore, the excess of Th17 cells and deficiency of Tregs could contribute to the pathologies observed in IBD. The discovery of an imbalance in Treg and Th17 cell numbers in IBD prompted further investigation of these cells in intestinal biopsies collected from IBD, coeliac and control subjects. Real time RT-PCR of intestinal biopsy samples demonstrated increased expression of the Th17 cytokine, IL-17a, in both IBD and coeliac disease. Elevated levels of the Treg transcription factor Foxp3 were also identified in intestinal biopsies from IBD subjects. It was therefore hypothesised that Treg cells may have been actively recruited from the periphery in an attempt to control inflammation in the gut; however, the intestinal cytokine microenvironment may have restricted the regulatory function of these cells. Cytokines known to promote human Th17 differentiation, namely IL-1β, IL-6, TGF-β, IL-21 and IL-23, were explored in intestinal biopsy samples from IBD, coeliac and control subjects. High levels of IL-1β and IL-6 were detected in IBD patient samples, however, no change in levels of IL-21 or IL-23 were observed in IBD or coeliac disease subjects. Elevated levels of TGF-β were only identified in UC. No changes in cytokine expression were observed between control and coeliac subjects, except a significant decrease in IL-6 levels was identified in coeliac disease sufferers. The pro-inflammatory microenvironment identified in intestinal biopsies from IBD subjects may have promoted the continual differentiation and development of Th17 cells, whilst restricting Treg activity. Moreover, the observed deficiency of Treg in IBD patients may have impaired the ability of the immune system to limit excessive pathogenic Th17 driven immune responses in the intestinal mucosa. Therefore, therapeutic approaches that aim to re-establish regulatory and effector cell homeostasis by increasing Treg numbers in IBD patients, and specifically targeting Th17 cells, may prove effective in the treatment of IBD. Approaches such as these could provide greater focus to treatment strategies for IBD management compared to current broad-spectrum immunosuppressive therapies that could increase susceptibility to cancer or infection in IBD patients. In addition, the imbalance of regulatory and effector cells demonstrated in the peripheral blood of IBD patients may potentially provide new options for a noninvasive diagnostic tool. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1457580 / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2009

Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) and coeliac disease are debilitating gastrointestinal diseases that seriously affect the quality of life of those affected. Under normal circumstances, the intestinal immune system is maintained in a state of controlled inflammation, whereby balance exists between protective immunity, mediated by effector cells, and tolerance mediated by cells with regulatory function. However, an aberrant immune response is believed to contribute to the intestinal inflammation present in individuals afflicted by these diseases. This thesis investigated the involvement of CD4⁺ CD25[superscript]high Foxp3⁺ Regulatory T cells (Treg) and Th17 Effector cells in both inflammatory bowel disease (IBD) and coeliac disease. The reciprocal relationship between Treg and Th17 cells under certain cytokine conditions, has prompted the exploration of these two cell types in IBD and coeliac disease. Previous studies have examined these factors individually in a range of diseases, however, to our knowledge the study of both Treg and Th17 in IBD and coeliac disease subjects represents a novel area of research. Crohn’s disease (CD), ulcerative colitis (UC) and coeliac disease subjects were recruited through the Department of Gastroenterology and Hepatology at The Queen Elizabeth Hospital (QEH) in Adelaide, South Australia. In total, one-hundred and seventeen subjects were enlisted in this study to donate blood samples. In addtion, intestinal biopsy samples were collected from fifty-six subjects undergoing colonoscopy at the QEH Department of Gastroenterology and Hepatology. All subjects participated, with informed consent and ethics approval. Treg and Th17 cell numbers were investigated in the peripheral blood of Crohn’s disease, ulcerative colitis, coeliac disease and control subjects using multi-colour, intracellular flow cytometry. A decrease in Treg cell numbers and an increase in Th17 cell numbers was observed in IBD, but not in coeliac disease. Closer investigation into the ratio of Treg and Th17 cells within patients identified a near 1:1 Treg/Th17 ratio in control subjects, but a lower Treg/Th17 ratio in IBD patients. This suggested a disturbance in regulatory and effector cell equilibrium. Furthermore, the excess of Th17 cells and deficiency of Tregs could contribute to the pathologies observed in IBD. The discovery of an imbalance in Treg and Th17 cell numbers in IBD prompted further investigation of these cells in intestinal biopsies collected from IBD, coeliac and control subjects. Real time RT-PCR of intestinal biopsy samples demonstrated increased expression of the Th17 cytokine, IL-17a, in both IBD and coeliac disease. Elevated levels of the Treg transcription factor Foxp3 were also identified in intestinal biopsies from IBD subjects. It was therefore hypothesised that Treg cells may have been actively recruited from the periphery in an attempt to control inflammation in the gut; however, the intestinal cytokine microenvironment may have restricted the regulatory function of these cells. Cytokines known to promote human Th17 differentiation, namely IL-1β, IL-6, TGF-β, IL-21 and IL-23, were explored in intestinal biopsy samples from IBD, coeliac and control subjects. High levels of IL-1β and IL-6 were detected in IBD patient samples, however, no change in levels of IL-21 or IL-23 were observed in IBD or coeliac disease subjects. Elevated levels of TGF-β were only identified in UC. No changes in cytokine expression were observed between control and coeliac subjects, except a significant decrease in IL-6 levels was identified in coeliac disease sufferers. The pro-inflammatory microenvironment identified in intestinal biopsies from IBD subjects may have promoted the continual differentiation and development of Th17 cells, whilst restricting Treg activity. Moreover, the observed deficiency of Treg in IBD patients may have impaired the ability of the immune system to limit excessive pathogenic Th17 driven immune responses in the intestinal mucosa. Therefore, therapeutic approaches that aim to re-establish regulatory and effector cell homeostasis by increasing Treg numbers in IBD patients, and specifically targeting Th17 cells, may prove effective in the treatment of IBD. Approaches such as these could provide greater focus to treatment strategies for IBD management compared to current broad-spectrum immunosuppressive therapies that could increase susceptibility to cancer or infection in IBD patients. In addition, the imbalance of regulatory and effector cells demonstrated in the peripheral blood of IBD patients may potentially provide new options for a noninvasive diagnostic tool. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1457580 / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2009

Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) and coeliac disease are debilitating gastrointestinal diseases that seriously affect the quality of life of those affected. Under normal circumstances, the intestinal immune system is maintained in a state of controlled inflammation, whereby balance exists between protective immunity, mediated by effector cells, and tolerance mediated by cells with regulatory function. However, an aberrant immune response is believed to contribute to the intestinal inflammation present in individuals afflicted by these diseases. This thesis investigated the involvement of CD4⁺ CD25[superscript]high Foxp3⁺ Regulatory T cells (Treg) and Th17 Effector cells in both inflammatory bowel disease (IBD) and coeliac disease. The reciprocal relationship between Treg and Th17 cells under certain cytokine conditions, has prompted the exploration of these two cell types in IBD and coeliac disease. Previous studies have examined these factors individually in a range of diseases, however, to our knowledge the study of both Treg and Th17 in IBD and coeliac disease subjects represents a novel area of research. Crohn’s disease (CD), ulcerative colitis (UC) and coeliac disease subjects were recruited through the Department of Gastroenterology and Hepatology at The Queen Elizabeth Hospital (QEH) in Adelaide, South Australia. In total, one-hundred and seventeen subjects were enlisted in this study to donate blood samples. In addtion, intestinal biopsy samples were collected from fifty-six subjects undergoing colonoscopy at the QEH Department of Gastroenterology and Hepatology. All subjects participated, with informed consent and ethics approval. Treg and Th17 cell numbers were investigated in the peripheral blood of Crohn’s disease, ulcerative colitis, coeliac disease and control subjects using multi-colour, intracellular flow cytometry. A decrease in Treg cell numbers and an increase in Th17 cell numbers was observed in IBD, but not in coeliac disease. Closer investigation into the ratio of Treg and Th17 cells within patients identified a near 1:1 Treg/Th17 ratio in control subjects, but a lower Treg/Th17 ratio in IBD patients. This suggested a disturbance in regulatory and effector cell equilibrium. Furthermore, the excess of Th17 cells and deficiency of Tregs could contribute to the pathologies observed in IBD. The discovery of an imbalance in Treg and Th17 cell numbers in IBD prompted further investigation of these cells in intestinal biopsies collected from IBD, coeliac and control subjects. Real time RT-PCR of intestinal biopsy samples demonstrated increased expression of the Th17 cytokine, IL-17a, in both IBD and coeliac disease. Elevated levels of the Treg transcription factor Foxp3 were also identified in intestinal biopsies from IBD subjects. It was therefore hypothesised that Treg cells may have been actively recruited from the periphery in an attempt to control inflammation in the gut; however, the intestinal cytokine microenvironment may have restricted the regulatory function of these cells. Cytokines known to promote human Th17 differentiation, namely IL-1β, IL-6, TGF-β, IL-21 and IL-23, were explored in intestinal biopsy samples from IBD, coeliac and control subjects. High levels of IL-1β and IL-6 were detected in IBD patient samples, however, no change in levels of IL-21 or IL-23 were observed in IBD or coeliac disease subjects. Elevated levels of TGF-β were only identified in UC. No changes in cytokine expression were observed between control and coeliac subjects, except a significant decrease in IL-6 levels was identified in coeliac disease sufferers. The pro-inflammatory microenvironment identified in intestinal biopsies from IBD subjects may have promoted the continual differentiation and development of Th17 cells, whilst restricting Treg activity. Moreover, the observed deficiency of Treg in IBD patients may have impaired the ability of the immune system to limit excessive pathogenic Th17 driven immune responses in the intestinal mucosa. Therefore, therapeutic approaches that aim to re-establish regulatory and effector cell homeostasis by increasing Treg numbers in IBD patients, and specifically targeting Th17 cells, may prove effective in the treatment of IBD. Approaches such as these could provide greater focus to treatment strategies for IBD management compared to current broad-spectrum immunosuppressive therapies that could increase susceptibility to cancer or infection in IBD patients. In addition, the imbalance of regulatory and effector cells demonstrated in the peripheral blood of IBD patients may potentially provide new options for a noninvasive diagnostic tool. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1457580 / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2009

Introduction: Recent findings about the pathogenesis of glaucoma have already demonstrated the presence of some specific autoimmune mechanisms. It has also been shown that autoimmune diseases often manifest in co-occurrence, such as celiac disease and type 1 diabetes mellitus or psoriasis. This association can be explained by sharing some of the risk variants of HLA molecules class II. Considering glaucoma an autoimmune disease, the question raises how the glaucoma genetic risk factors affect the phenotype of another autoimmune disease or vice versa, whether genetic risk variants associated for example with celiac disease can affect the glaucoma phenotype. Aims: The aims of this study were to i) identify possible genetic risk markers associated with the development of glaucoma, based on the available literature, and to map their occurrence among members of a three-generation family suffering from glaucoma and multiple autoimmune diseases, ii) find carriers of HLA-DQ2/DQ8 among the members of the same family, iii) verify whether an individual's genotype correlates with his/her phenotype, and iv) determine the potential effect of specific HLA alleles on the glaucoma phenotype. Material and methods: This study used DNA samples derived from 34 members of a three-generation family, in which coeliac...

Bakgrund Celiaki är en autoimmun sjukdom som ger inflammation i tunntarmsslemhinnan vid intag av gluten. Symtom hos vuxna kan vara diffusa och därför svåra att koppla till celiaki. I Sverige är genomsnittstiden från första symtom till celiakidiagnos ungefär 10 år och det finns luckor i kunskapen om vilka konsekvenser fördröjningen till diagnos ger. Syfte Studiens syfte är att överblicka hur fördröjd diagnos av celiaki hos vuxna påverkar samhällets resurser, hur dessa individer upplever att symptomen påverkat deras sociala liv före och efter diagnos, samt om diagnostiken behöver effektiviseras. Metod I Sverige, september 2012, skickades en Internetbaserad enkät ut till 4337 medlemmar i Svenska Celiakiförbundet varav 611 kvarstod efter bortfall. Enkätens fokus var främst sjukfrånvaro, vårdkontakter och social påverkan p.g.a. symtom av celiaki. Enkäterna analyserades i SPSS (v.20.0) med p<0,05. Resultat Efter diagnos sjönk både sjukfrånvaro och vårdkontakter. Deltagarna undvek också sociala aktiviteter i mindre utsträckning och majoriteten upplevde förbättrad livskvalité. En stor del (39 %, n=238) uppgav att de fått diagnos först 10 år eller mer efter symtomdebut, varav majoriteten var äldre. Det var framför allt de som uppgav en fördröjning på fyra år eller mer från första symtom till diagnos som upplevde att deras livskvalité förbättrades av diagnosen. Slutsats Det är viktigt att celiakidiagnos ställs tidigt för att bespara kostnader som annars kommer av sjukfrånvaro och vårdkonsumtion, samt minska den negativa påverkan av symtom på det sociala livet och livskvalitén. Då mer än hälften av deltagarna i studien haft symtom i minst 5 år innan diagnos anser vi att åtgärder måste sättas in. Tidigare diagnos kräver antingen screening av befolkningen eller nya vårdplaner där diffusa symtom av celiaki uppmärksammas mer. Mer studier behövs för att avgöra vilken åtgärd som är mest hållbar. / Background Coeliac disease is an autoimmune disease where gluten causes inflammation in the mucosa of the small intestine. Symptoms in adults may be vague and therefore difficult to associate with coeliac disease. In Sweden, the average delay from first symptom to diagnosis is about 10 years. There are gaps in the knowledge of the consequences of a delayed diagnose. Objective The purpose of this study is to review the effect of the delay of coeliac diagnosis among adults on society’s resources, how the symptoms may have affected these individuals social life and the need of improved diagnosis. Method In Sweden, September 2012, an online questionnaire was distributed to 4,337 members of the Swedish Coeliac Society of which 611 was included in the study. The survey focus was mainly sick leave, health care contacts and social impacts due to symptoms of coeliac disease. The questionnaires were analyzed in SPSS (v.20.0) with p<0,05. Results Both sick leave and health care contacts decreased after diagnosis. The participants also avoided social activities to a lower extent and the majority experienced an improved quality of life. A large proportion (39%, n=238) reported that diagnosis delayed at least 10 years from the onset of symptoms, the majority of whom were older than the average. It was mainly those who reported a long delay from first symptom to diagnosis who experienced an improvement in quality of life due to diagnosis. Conclusion Early diagnosis is important in order to reduce costs that would otherwise derive from health care consumption and sick leave. Early diagnosis would also reduce the negative impact of symptoms on social life and quality of life. Since the majority of the participants reported a delay of at least 5 years from onset of symptoms to diagnosis, we believe that it is necessary to take action. In order to diagnose individuals with coeliac disease at an earlier stage it is necessary to apply effective methods such as screening or new care plans with more attention on vague symptoms. To determine which method is most sustainable, more studies needs to be done.

Background Mass screening for celiac disease (CD) as a public health intervention is controversial. Before implementation, a suitable screening strategy should be outlined, and the acceptability of the screening scrutinized. Also, the benefits of early detection and possible negative consequences should be explored and compared. The overall aim of this thesis was to evaluate different strategies for finding 12-year-olds with undiagnosed CD in the general population, and to explore the experiences of those receiving the diagnosis in a mass screening. Methods A school-based CD screening of 12-year-olds was conducted in five study sites across Sweden. Out of 10041 children who were invited, 7208 had a blood sample analyzed for CD-marker tissue transglutaminase of isotype IgA (tTG-IgA) and 7161 for total serum IgA (s-IgA). If the s-IgA value was low, tTG-IgG was also measured. Additional analysis of endomysial antibodies (EMA) was performed if borderline values of tTG were found. In total, 192 had elevated CD-markers, 184 underwent a small intestinal biopsy and 153 eventually had CD diagnosed. Before receiving knowledge about their CD status, children and their parents filled in questionnaires regarding symptoms and CD-associated conditions. Questionnaires were returned by 7054 children (98%) and 6294 parents (88%). Later, all adolescents who had been diagnosed with CD more than one year ago (n=145), and their parents, were invited to a mixed-method follow-up study in which they shared their experiences in questionnaires, written narratives and focus group discussions. In total, we have information on 117 (81%) of these adolescents, either from the adolescents themselves (n=101) and/or from their parent/s (n=125). Data were analyzed using a combination of descriptive and analytical quantitative and qualitative methodologies. Results We found that information on symptoms and CD-associated conditions were poor predictors for finding undiagnosed CD in the study population. Questionnaire-based case-finding by asking for CD-associated symptoms and conditions would have identified 52 cases (38% of all cases) at a cost of blood-sampling 2282 children (37% of the study population). The tTG-IgA test had an excellent diagnostic accuracy with the area under the receiver operating characteristic curve of 0.988. If using the recommended cut-off for tTG-IgA (>5 U/mL) 151 had fulfilled biopsy criteria and 134 CD cases had been identified. The strategy of lowering the cut-off to tTG-IgA>4 U/mL, and adding the EMA analysis in those with tTG-IgA between 2-4 U/mL, identified another 17 cases (a 12% increase) at the cost of performing 32 additional biopsies. Measuring total s-IgA in 7161 children discovered only two additional cases at the cost of performing 5 additional biopsies. The positive predictive value of our screening strategy was 80%.  Results from the follow-up study of the screening-detected CD cases illustrated that 54% reported health improvement after initiated treatment, but also that these health benefits had to be balanced against social sacrifices. We also found that although the screening-detected diagnosis was met with surprise and anxiety, the adolescents and their parents were grateful for being made aware of the diagnosis. A majority of parents (92%) welcomed a future screening, but both adolescents and parents suggested that it should be conducted earlier in life. Conclusion Obtaining information on symptoms and CD-associated conditions was not a useful step in finding undiagnosed CD cases in a general population. The serological marker tTG-IgA, however, had excellent diagnostic accuracy also when lowering the cut-off. The diagnosis had varying impact on adolescents’ quality of life, and their perceived change in health had to be balanced against the social sacrifices resulting from the diagnosis. Overall, CD mass screening seemed acceptable to most of those who were diagnosed and their parents.

Ziel dieser Arbeit war es, in Querschnitts- und prospektiven Longitudinalstudien die Diagnostik diabetes-assoziierter Autoimmunerkrankungen (Autoimmun-Thyreoiditis und Zöliakie, primäre Komorbiditäten) sowie diagnostische Verfahren zur Früherkennung von sekundären Spätkomplikationen (Retinopathie und Nephropathie, sekundäre Komorbiditäten) bei Kindern und Jugendlichen mit Typ 1 Diabetes zu evaluieren. Mit Hilfe eines Screenings spezifischer Antikörper (EmA, IgA-Gliadin-, IgA-tTG-Antikörper) konnte eine höhere als bisher berichtete Zöliakie-Prävalenz bei zwei Prozent der asymptomatischen Kinder mit Typ 1 Diabetes festgestellt werden. Eine Autoimmun-Thyreoiditis wurde durch Untersuchungen von Schilddrüsen-spezifischen Antikörpern (Anti-TPO, Anti-TG) bei bis zu 20 Prozent der Kinder und Jugendlichen diagnostiziert. Mädchen hatten signifikant häufiger Schilddrüsen-Antikörper als Jungen. Mit zunehmendem Alter der Patienten stieg die Prävalenz der Antikörper. Die Anwesenheit positiver Schilddrüsen-Antikörper war mit höheren TSH-Werten assoziiert. Sehr hohe Schilddrüsen-Antikörper (Anti-TPO, Anti-TG) waren prädiktiv für die spätere Entwicklung einer subklinischen Hypothyreose. Hinsichtlich der sekundären Komorbiditäten konnte anhand von Messungen der glomerulären (Alb, Tf, IgG) und tubulären Marker (NAG, alpha1-MG) nachgewiesen werden, dass bei Patienten mit Diabetes nicht nur eine glomeruläre, sondern auch eine tubuläre renale Dysfunktion vorliegen kann. Eine erhöhte NAG-Urinausscheidung war prädiktiv für die Entwicklung einer Mikroalbuminurie. Für die Retinopathieentwicklung war die Stoffwechseleinstellung (HbA1c) von wesentlicher Bedeutung, insbesondere während der ersten Diabetesjahre. In der Pubertät kam es zu einer Beschleunigung der Retinopathieentwicklung. Weitere Risikofaktoren für sekundäre Spätkomplikationen insbesondere Retinopathie waren Blutdruck, Lipidstoffwechsel (Triglyzeride, HDL-Cholesterin) und Gesamtrenin. Für die Prognose und Prävention primärer und sekundärer Komorbiditäten bei Kindern mit einem Typ 1 Diabetes als chronische Grunderkrankung ist ein frühzeitiges und regelmäßiges Screening von wesentlicher Bedeutung. / The aim of this study was the evaluation of diagnostic procedures for the early detection of diabetes-associated autoimmune diseases (autoimmune thyroiditis and coeliac disease, primary co-morbidity) as well as of diabetes-specific late complications (retinopathy and nephropathy, secondary co-morbidity) in children and adolescents with type 1 diabetes. The prevalence of coeliac disease among asymptomatic children with type 1 diabetes was 2 percent based on a screening for specific autoantibodies (EMA, IgA-gliadin-, IgA-tTG-antibodies) being higher than reported previously. Autoimmune thyroiditis was diagnosed in up to 20 percent of children and adolescents according to screening procedures for thyroid-specific antibodies (anti-TPO, anti-TG). Girls had more frequently thyroid antibodies than boys. The prevalence of thyroid antibodies increased with increasing age of patients. The presence of thyroid antibodies was associated with higher TSH values, while very high values of thyroid antibodies were predictive for the development of a subclinical hypothyroidism. Studies concerning the prevalence of secondary co-morbidity in young patients with type 1 diabetes revealed that not only glomerular, but also tubular renal dysfunction may occur in these patients. These studies based on the measurement of urinary excretion of glomerular (Alb, Tf, IgG) and tubular (NAG, alpha1-MG) markers. Elevated urinary excretion of NAG was predictive for the development of microalbuminuria. Glycaemic control (HbA1c), particularly during the first years of diabetes, constituted a significant parameter for the development of retinopathy, while puberty may accelerate the development of this late complication. Arterial blood pressure, lipid profile (triglycerides, HDL-cholesterol) and total renin had been found to be additional risk factors for the development of late complications, particularly retinopathy. An early and regularly performed screening is recommended for the prognosis and prevention of primary and secondary co-morbidity in children with type 1 diabetes.

<p>Coeliac disease (CD) is a gluten intolerance condition that results in the flattening of the villi, which line the bowel. It is the most common cause of malabsorption of food nutrients. This inability to absorb sufficient levels of nutrients causes many of the common symptoms experienced by CD patients. Some of the symptoms, which lead to an increase in mortality rate, include chronic diarrhea, fatigue, iron-deficient anemia and osteoporosis. People with CD have higher than normal levels of certain antibodies in their blood. Thus, the concentration of anti-transglutaminase antibody (anti-tTG) in human sera is an important analytical marker for the diagnosis of CD. An immunosensor is a type of biosensor that has an antigen or antibody fragment as its biological recognition component. The specificity of the molecular recognition of antigens by antibodies to form a stable complex is the basis of immunosensor technology. In this work, overoxidized polypyrrole (OvoxPpy) was electrosynthesized as a noval sensor platform on a glassy carbon electrode (GCE). The OvoxPpy was then doped with gold-nanoparticles (GNP) by electrodeposition using cyclic voltammetry to form GNP|OvoxPpy||GCE electrode system. Morphology and size of the GNP|OvoxPpy||GCE nanocomposite were determined using scanning electron microscopy. The electrochemical immunosensor for anti-tTG antibodies was prepared by immobilizing transglutaminase antigen (tTG-antigen) onto the GNP|OvoxPpy||GCE by drop coating and allowed to incubate for 2 hrs. The electrochemical characterization of the nanocomposite platform and immunosensor were studied by voltammetry and electrochemical impedance spectroscopy (EIS)...</p>

<p>Coeliac disease (CD) is a gluten intolerance condition that results in the flattening of the villi, which line the bowel. It is the most common cause of malabsorption of food nutrients. This inability to absorb sufficient levels of nutrients causes many of the common symptoms experienced by CD patients. Some of the symptoms, which lead to an increase in mortality rate, include chronic diarrhea, fatigue, iron-deficient anemia and osteoporosis. People with CD have higher than normal levels of certain antibodies in their blood. Thus, the concentration of anti-transglutaminase antibody (anti-tTG) in human sera is an important analytical marker for the diagnosis of CD. An immunosensor is a type of biosensor that has an antigen or antibody fragment as its biological recognition component. The specificity of the molecular recognition of antigens by antibodies to form a stable complex is the basis of immunosensor technology. In this work, overoxidized polypyrrole (OvoxPpy) was electrosynthesized as a noval sensor platform on a glassy carbon electrode (GCE). The OvoxPpy was then doped with gold-nanoparticles (GNP) by electrodeposition using cyclic voltammetry to form GNP|OvoxPpy||GCE electrode system. Morphology and size of the GNP|OvoxPpy||GCE nanocomposite were determined using scanning electron microscopy. The electrochemical immunosensor for anti-tTG antibodies was prepared by immobilizing transglutaminase antigen (tTG-antigen) onto the GNP|OvoxPpy||GCE by drop coating and allowed to incubate for 2 hrs. The electrochemical characterization of the nanocomposite platform and immunosensor were studied by voltammetry and electrochemical impedance spectroscopy (EIS)...</p>