Abstract Increased prevalence of anticardiolipin antibodies (aCL) and antinuclear antibodies (ANA) and changes in serum immunoglobulin concentrations have been reported in patients with epilepsy. The purpose of this study was to determine the presence of aCL, ANA, anti-B2 glycoprotein I -antibodies (anti-B2-GPI), antimitochondrial antibodies (AMA), immunoglobulin A, G and M serum concentrations and the presence of IgA and IgG class antigliadin antibodies (AGAbA and AGAbG), transglutaminase antibodies (tTGAbA) and antiendomysial antibodies (EMA) in a cohort of 1386 adult patients treated for epilepsy in the Oulu University Central Hospital during the years 1996–7 and in a reference population obtained from the Population Register Centre and matched for age, gender and municipality of residence. The effects of co-morbidity, medications, age, gender and different epilepsy attributes on the occurrence of the immunological parameters studied as well as the possible interrelations of these parameters were studied. There was no difference in the presence of aCL or ANA between the patients and the reference subjects. In patients, aCL were associated with long duration of epilepsy and poor seizure control. Low IgA serum concentrations were more common in patients with epilepsy, particularly those using phenytoin. Unspecific AMA were more common among the epilepsy patients. The prevalence of coeliac disease (CD)-related antibodies was similar in patients with epilepsy and in the reference population. AGAbA were associated with primary generalised epilepsy. No significant interrelations between the immunological markers were found. These findings suggest that patients with epilepsy do not have an increased prevalence of autoantibodies as a result of their disease. Various factors such as genetic traits and epilepsy attributes may independently affect the presence of each individual immunological marker.

La enfermedad celíaca (EC) es una inflamación del intestino delgado, que afecta a individuos genéticamente susceptibles, provocada por la ingestión de algunos cereales. La prevalencia de EC en Europa y los EE.UU. es de aproximadamente 1%. La mayoría de los casos de CD sin diagnosticar durante muchos años porque de espectro clínico es muy variable y presentación atípica. La prueba estándar de oro para el diagnóstico de EC es la biopsia del intestino delgado, una prueba invasiva y costosa. Fuerte relación entre la CD y antígenos leucocitarios humanos (HLA) se ha demostrado, con un 95% de los pacientes con EC portadores del antígeno HLA DQ2 heterodímero y el 5% llevan DQ8 heterodímero. Personas negativos DQ2 y DQ8 han demostrado ser muy poco probable que desarrollen CD. El objetivo general de la tesis es el desarrollo de una manera rápida, fácil de utilizar, rentable matriz genosensor de diagnóstico para DQ2/DQ8 escribir como una herramienta de diagnóstico para la predisposición de CD. Dos métodos diferentes han sido investigados en paralelo. En el primer método, la matriz genosensor se desarrolló empleando el método SSOP, mediante el diseño de sondas diferentes alelos específicos. Mientras que en el segundo enfoque, la técnica SSP explotar un nuevo enfoque para la detección directa y rápida de una doble cadena de amplificación de PCR se investigó. En ambos métodos, condiciones de ensayo fueron optimizadas y finalmente el análisis de muestras clínicas reales se realizó. / Coeliac disease (CD) is a small intestinal inflammation, affecting genetically susceptible individuals, triggered by ingestion of certain cereals. Prevalence of CD in Europe and US is about 1%. Most of CD cases remain undiagnosed for many years because of highly variable clinical spectrum and atypical presentation. The gold standard test for CD diagnosis is the small-intestinal biopsy, an invasive and expensive test. Strong relation between CD and Human Leukocyte Antigens (HLA) has been proved, as 95% of the CD patients carrying HLA DQ2 heterodimer and 5% carrying DQ8 heterodimer. DQ2 and DQ8 negative individuals have been shown to be very unlikely to develop CD. The overall objective of the thesis is to develop a rapid, ease to use, cost effective diagnostic genosensor array for DQ2/DQ8 typing as a diagnostic tool for CD predisposition. Two different methods have been investigated in parallel. In the first method, the genosensor array was developed employing the SSOP method, by designing different allele specific probes. Whilst in the second approach, the SSP technique exploiting a novel approach for the direct and rapid detection of a double stranded PCR amplicon was investigated. In both approaches, assay conditions were optimised and finally analysis of real clinical samples was performed.

Coeliac disease is a chronic enteropathy triggered by gluten. Patients produce antibodies to gliadin and the autoantigen tissue transglutaminase (tTG). These anti-tTG autoantibodies are disease specific and used in diagnosis. The autoantibodies can be detected by immunofluorescence (the endomysial antibody tests) or by ELISA using recombinant tTG. In vivo tTG associates with fibronectin, which may account for the greater sensitivity of the endomysial antibody assay compared to the ELISA. This project had two aims:  to determine whether GST-tagged tTG bound fibronectin and then, using the fibronectin bound tTG, whether a two-tiered ELISA increased anti-tTG binding in coeliac disease patients. First fibronectin was coupled to a solid support and then incubated with tTG. This was then analysed using SDS-PAGE. Secondly, an ELISA with a two-tiered antigen coating was created by coupling tTG to Fn. This mimics the in vivo orientation of the antigen and could theoretically increase anti-tTG binding. Comparative ELISAs were then run to see if anti-tTG binding differed between tTG and fibronectin-coupled tTG antigen coatings. Results showed GST-tagged tTG bound fibronectin. Coupling of tTG to fibronectin gave no improved binding of anti-tTG. On the contrary, most patients tested had decreased anti-tTG binding compared to the normal tTG based ELISA.

<p>Coeliac disease (CD) is a multifactorial disease of the small intestine. In genetically predisposed individuals the, ingestion of cereals leads to a remodulation of the mucosal architecture, and the production of autoantibodies against tissue transglutaminase (tTG). The treatment is a lifelong gluten-free diet.</p><p>The diagnostic procedure relies on the examination of a small-bowel biopsy that displays villous atrophy. A spectrum of clinical manifestations is associated with CD, ranging from overt enteropathy to atypical and silent symptoms. Approximately 1% of the general population has CD, and the majority is undiagnosed. Although most patients with active CD can be detected by the assessment of elevated IgA-tTG, some patients lack these antibodies. Moreover, individuals with IgA-deficiency cannot be identified by means of IgA serology. </p><p>The aim of this thesis was to investigate the clinical utility of IgG-tTG for the detection and follow-up of subjects with active CD. The included studies showed that IgG-tTG was highly prevalent in IgA-deficient and IgA-competent patients with CD, whereas non-CD patients rarely had these antibodies. During a gluten-free diet, IgG-tTG decreased, demonstrating that IgG-tTG can be used to follow the patient’s adherence such a diet. Furthermore, 10% of healthy IgA deficient blood donors had elevated IgG-tTG, indicating that they had silent CD. </p><p>In IgA-competent subjects, high IgG-tTG levels correlated with a severe mode of CD and profound mucosal deterioration, suggesting that IgG-tTG might be involved in the disease progression. Moreover, we found that although a considerable percentage of IgA-competent patients lack IgG-tTG, the presence of these antibodies in conjunction with high levels of IgA-tTG was highly predictive of a severe small-intestine villous atrophy. It was also demonstrated that IgG-tTG normalisation coincided with clinical remission in IgA-competent CD patients on a gluten-free diet. </p>

Coeliac disease (CD) is a multifactorial disease of the small intestine. In genetically predisposed individuals the, ingestion of cereals leads to a remodulation of the mucosal architecture, and the production of autoantibodies against tissue transglutaminase (tTG). The treatment is a lifelong gluten-free diet. The diagnostic procedure relies on the examination of a small-bowel biopsy that displays villous atrophy. A spectrum of clinical manifestations is associated with CD, ranging from overt enteropathy to atypical and silent symptoms. Approximately 1% of the general population has CD, and the majority is undiagnosed. Although most patients with active CD can be detected by the assessment of elevated IgA-tTG, some patients lack these antibodies. Moreover, individuals with IgA-deficiency cannot be identified by means of IgA serology. The aim of this thesis was to investigate the clinical utility of IgG-tTG for the detection and follow-up of subjects with active CD. The included studies showed that IgG-tTG was highly prevalent in IgA-deficient and IgA-competent patients with CD, whereas non-CD patients rarely had these antibodies. During a gluten-free diet, IgG-tTG decreased, demonstrating that IgG-tTG can be used to follow the patient’s adherence such a diet. Furthermore, 10% of healthy IgA deficient blood donors had elevated IgG-tTG, indicating that they had silent CD. In IgA-competent subjects, high IgG-tTG levels correlated with a severe mode of CD and profound mucosal deterioration, suggesting that IgG-tTG might be involved in the disease progression. Moreover, we found that although a considerable percentage of IgA-competent patients lack IgG-tTG, the presence of these antibodies in conjunction with high levels of IgA-tTG was highly predictive of a severe small-intestine villous atrophy. It was also demonstrated that IgG-tTG normalisation coincided with clinical remission in IgA-competent CD patients on a gluten-free diet.

The Thesis consists of the theoretical and research part. The theoretical part of the Thesis deals with the anatomy and physiology of the small intestine of the child. It also brings detailed characteristics of celiac disease and for the sake of interest we mentioned the interesting history of coeliac disease. Furthermore, we focus on the types, symptoms, diagnosis, treatment and complications of celiac disease. Substantial part is devoted to nutrition, where we focus on its basic elements and, gradually, we walk through proper nutrition in children. In descending order we go through individual child periods, from infancy to adolescence, mentioning what nutrition is the best for the particular age period. The next chapter gives the detailed description of the gluten-free diet which must be kept by the coeliac patients during all of their lives. Research part of the Thesis is processed using the quantitative strategy. The objective of the Thesis was to find out which problems the coeliac children appearing at the paediatric gastroenterologist and the general practitioner for children and adolescents suffer from, as well as the assessment of these problems using nursing diagnosis: 0002 Imbalanced nutrition: less than the organism needs. The second objective of the Thesis was to determine differences in the incidence of celiac disease in children by sex and age when diagnosing this disease. The objectives faced 2 hypotheses. H1: There is a difference in the incidence of determining the signs and related factors in children registered in gastroenterology clinics and general paediatricians. H 2: The incidence of celiac disease will be higher in girls than in boys. To collect data, we chose a content analysis of documents, in our case, analysis of medical records of children at a gastroenterology outpatient department and at a general practitioner for children and adolescents. The data were being collected in the period from January to February 2014. The survey was conducted at the paediatric gastroenterology office of MUDr. Ivana Ženíšková in České Budejovice and at the general practitioner's office for children and adolescents of MUDr. Zdeňka Soukopová in Náměšt nad Oslavou. So as to process the research data we developed a research form - a record sheet, which contained 24 defining characters and 6 related factors from the nursing diagnose: 0002 Imbalanced nutrition: less than the organism needs. Furthermore, the research form included some demographic data: age, sex, home address, family predispositions, duration of breastfeeding, cage of the child at the introduction of complementary feeding, age when the disease is diagnosed, and what foods were first administered to the child. Another point we decided to include in the research form was the defining characteristics and related factors supplemented from the medical records of children. When processing the research data we used the linear method and recorded frequency of the incidence. The results of NANDA diagnoses validation were processed according to Fehring's DCV where we calculated the arithmetic mean, assigned appropriate values and included them in summary tables. The values in the tables are marked in colours, where the green colour marked very significant characteristics according to Fehring and the red one marked very little significant characteristics according to Fehring.

Abstract Nutritional status affects every aspect of a child?s health. Thorough nutritional assessment is hampered by the lack of a single comprehensive tool, which can cover all aspects of nutritional assessment. In three distinct studies, this thesis investigated the nutritional status of hospitalised children, children with coeliac disease and children with inflammatory bowel disease. Study 1 The objectives of this study were to assess prevalence of malnutrition and nutritional risk, and define demographic and anthropometric factors associated with nutritional risk among hospitalized children. In this cross sectional study, 157 hospitalised children were assessed for nutritional status using nutritional risk score (NRS) and anthropometric measurements. We found that 4.5%, 8.9%, 15.1% and 10.4% children were wasted, stunted, overweight and obese respectively. However, with the NRS, 47.8% of the children were at high nutritional risk. These children at high risk had lower weight for age (p=0.02), lower BMI percentiles for age (p=0.001) and longer hospitalization (p=0.001) than children at no risk. Study 2 The objectives of this study were to determine nutritional parameters in children with coeliac disease. Twenty-five children with coeliac disease and an equal number of age and gender matched controls were enrolled and anthropometric measurements, BIA and leptin levels were analysed in all. No significant differences were found between the children with coeliac disease and controls in these parameters. BMI percentile correlated with leptin levels in children with coeliac disease. Study 3 The objectives of this study were to determine anthropometric parameters and leptin levels in children with IBD and ascertain if BMI correlates with leptin levels in these children. Thirty children with IBD and 60 age and gender matched controls were enrolled. Anthropometric measurements and leptin levels were analysed and compared with controls. IBD children had significantly low weight for age (p=0.002), BMI percentiles (p=0.001) and leptin levels (p=0.009) compared to controls. There was a correlation between BMI and leptin levels in IBD children. In conclusion, this thesis has shown that one quarter of hospitalized children were overweight or obese, and further, that half of the hospitalised children were at high risk of nutritional deterioration and these children had longer hospital stay than children at no risk. Children with coeliac disease had similar anthropometric measurements, body compartments and leptin levels to controls. However, children with IBD had lower anthropometric measurements and leptin levels, indicating under-nutrition. Nutritional assessment should be a mandatory part of clinical management with nutritional status assessed by various tools including NRS, anthropometry, BIA and leptin levels.

Introduction: Studies show that women living in Sweden treated for coeliac disease have lower subjective health than other women. After showing signs of remission, adults who have coeliac disease and follow a gluten-free diet, are expected to handle the treatment without any further planned follow-up by health care. Aim: The overall aim of this thesis was to study aspects of living with coeliac disease in adults in the years beyond the diagnosis. Methods: Quantitative methods were used in Studies I, II and III. A qualitative content analysis was performed in Study IV. Results: The results show that women with coeliac disease have a lower level of well-being than men with coeliac disease. The women who have coeliac disease reported a high rate of gastrointestinal symptoms, although they followed a gluten-free diet, and they visited health care services more frequently than women who did not have coeliac disease. A low rate of gastrointestinal symptoms, a positive self-image and few comorbidity emerged as factors that positively affected well-being. Worries also seemed to be a companion of women diagnosed with coeliac disease in adulthood, typically evident when socializing with others. Conclusion: This thesis may provide evidence questioning the validity of declaring all women with coeliac disease showing a normalized intestinal mucosa to be in remission, and thus leaving them to self-management. Clinical implications: Health care professionals need to be aware of that the transition to a gluten-free life may vary for individuals. It does not seem enough to follow a gluten-free diet to reach a state of good well-being for all women. A major task for health care providers is therefore to support women with CD in reaching better subjective treatment outcomes. The results may also contribute to that health care system develops routines in order to optimise the care and treatment of these patients.

This thesis investigated the number and function of natural killer T-cells (NK T-cells) as a function of age, in coeliac disease, Crohn’s disease and ulcerative colitis. NK T-cells are a newly appreciated class of immune cells that are able to regulate the activity of the broader T-cell population. NK T-cells have been implicated in animal models of autoimmune disease and in human autoimmune disease. A subset of NK cells express the T-cell receptor (TCR) and are termed NK T-cells. In humans a further small subset of NK T-cells express an invariant TCR α chain (Vα24Jα18) and contain the immunoregulatory cell population that is distinguished from classical T-cells by promptly producing interleukin-4 (IL-4). Invariant NK T-cells (iNK T-cells) have the surface phenotype of Vα24+ Vβ11+ T-cells and express CD161+ NK markers. They are CD4+ (single positive; SP) or CD4- (double negative; DN), CD1d restricted and are α-galactosylceramide (α-GalCer) reactive. NKT cells have been implicated in numerous autoimmune disorders. Early work showed a major deficiency of NKT cell numbers in nonobese diabetic (NOD) mice, a well-established model of spontaneous, autoimmune T-cell mediated insulin-dependent diabetes. Both the number of NKT cells and function, as assessed by IL-4 release following TCR ligation, are dramatically reduced in NOD mice. NK T-cells have been implicated in other models of autoimmunity such as, experimental allergic encephalomyelitis (EAE). They have since been investigated and shown to be deficient in a number of human autoimmune diseases including, systemic sclerosis (SSc), and systemic lupus erythematosus (SLE), multiple sclerosis, atopic asthma, atopic dermatitis, rheumatoid arthritis, type 1 diabetes mellitus and scleroderma. The basis of the work presented within this thesis originated from the deficiency of NK T-cells in models of autoimmune diseases and human autoimmune diseases. The initial aim of this thesis was to investigate the phenotype and function of Vα24+ NK T-cells in normal healthy control subjects and with respect to age. The original aim was to investigate whether NK cells, T-cells, NK T-like cells and invariant NK T-cells (iNK T-cells) are deficient in coeliac disease, Crohn’s disease and/or ulcerative colitis. Blood was collected for flow cytometry from normal control subjects, subjects with coeliac disease, Crohn’s disease and ulcerative colitis. The number of circulating NK cells, T-cells, NK T-like cells and iNK T-cells was assessed by three-colour flow cytometry. Intracellular cytokine production was measured after in vitro anti-CD3/ anti-CD28 antibodies, gluten fraction 3 and PMA:ionomycin stimulation. Vα24+ T-cells were quantified in ileocolonic biopsies by immunofluorescence and as mRNA by relative and real-time PCR (RT-PCR). The number of circulating Vα24+ T-cells and iNK T-cells decrease with age in normal healthy control subjects. Cytokine production was also affected by age. The work of this thesis has identified a subpopulation of otherwise normal healthy individuals whom have normal numbers of circulating Vα24+ T-cells, reduced numbers of circulating Vα24+ Vβ11+ T-cells and consequently iNK Tcells. Circulating CD161+ NK cells, Vα24+ T-cells and the SP subset of Vα24+ Tcells were reduced in coeliac disease. The low numbers of circulating Vα24+ T-cells was independent of diet. The number of circulating Vα24+ Vβ11+ Tcells were reduced in coeliac disease, and as a consequence, the number of circulating Vα24+ Vβ11+ α-GalCer/CD1d tetramer+ and Vα24+ 6B11+ iNK T-cells were reduced. The deficiency of Vα24+ T-cells was not confined to the blood, but observed within the intestinal mucosa. Intestinal Vα24 mRNA expression from subjects with coeliac disease was reduced compared to levels in normal subjects as assessed by relative and RT-PCR. Thus, Vα24+ T-cells were deficient in coeliac disease both systemically and mucosally. Cytokine production by Vα24+ T-cells, 6B11+ and Vα24+ α-GalCer/CD1d tetramer+ iNK T-cells after 4 h in vitro anti-CD3 stimulation was also impaired in subjects with coeliac disease. Circulating CD56+, CD57+, CD94+, CD161+ NK cells were reduced in Crohn’s disease and ulcerative colitis. Vα24+ T-cells and the SP subset of Vα24+ T-cells were reduced in Crohn’s disease but not in ulcerative colitis. Circulating Vα24+ Vβ11+ T-cells, Vα24+ Vβ11+ α-GalCer/CD1d tetramer+ and Vα24+ 6B11+ iNK T-cells were deficient in both Cohn’s disease and ulcerative colitis. The deficiency of Vα24+ T-cells was also observed within the intestinal mucosa. Intestinal Vα24 mRNA expression from Crohn’s disease and ulcerative colitis was reduced compared to levels in normal subjects as assessed by relative and RT-PCR. Cytokine production by Vα24+ T-cells, 6B11+ and Vα24+ α-GalCer/CD1d tetramer+ iNK T-cells after 4 h in vitro anti-CD3 stimulation was impaired for subjects with Crohn’s disease and ulcerative colitis. In summary, Vα24+ T-cell number and function were affected by age. Further investigations are warranted to see if deficiency of this immunoregulatory population is associated with disease. The decrease and dysfunction in immunoregulatory cells, Vα24 T-cells and iNK T-cells could contribute to the pathogenesis of coeliac disease, Crohn’s disease and ulcerative colitis. Coeliac disease, Crohn’s disease and ulcerative colitis are polygenetic diseases in which environmental factors play a significant role in disease development and state. The reduced numbers of iNK T-cell along with their impaired function may only be two factors. Presumably, other factors are involved. Nevertheless, iNK T-cells offer a potential target for the therapeutic intervention of coeliac disease, ulcerative colitis and Crohn’s disease. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345088 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2008

This thesis investigated the number and function of natural killer T-cells (NK T-cells) as a function of age, in coeliac disease, Crohn’s disease and ulcerative colitis. NK T-cells are a newly appreciated class of immune cells that are able to regulate the activity of the broader T-cell population. NK T-cells have been implicated in animal models of autoimmune disease and in human autoimmune disease. A subset of NK cells express the T-cell receptor (TCR) and are termed NK T-cells. In humans a further small subset of NK T-cells express an invariant TCR α chain (Vα24Jα18) and contain the immunoregulatory cell population that is distinguished from classical T-cells by promptly producing interleukin-4 (IL-4). Invariant NK T-cells (iNK T-cells) have the surface phenotype of Vα24+ Vβ11+ T-cells and express CD161+ NK markers. They are CD4+ (single positive; SP) or CD4- (double negative; DN), CD1d restricted and are α-galactosylceramide (α-GalCer) reactive. NKT cells have been implicated in numerous autoimmune disorders. Early work showed a major deficiency of NKT cell numbers in nonobese diabetic (NOD) mice, a well-established model of spontaneous, autoimmune T-cell mediated insulin-dependent diabetes. Both the number of NKT cells and function, as assessed by IL-4 release following TCR ligation, are dramatically reduced in NOD mice. NK T-cells have been implicated in other models of autoimmunity such as, experimental allergic encephalomyelitis (EAE). They have since been investigated and shown to be deficient in a number of human autoimmune diseases including, systemic sclerosis (SSc), and systemic lupus erythematosus (SLE), multiple sclerosis, atopic asthma, atopic dermatitis, rheumatoid arthritis, type 1 diabetes mellitus and scleroderma. The basis of the work presented within this thesis originated from the deficiency of NK T-cells in models of autoimmune diseases and human autoimmune diseases. The initial aim of this thesis was to investigate the phenotype and function of Vα24+ NK T-cells in normal healthy control subjects and with respect to age. The original aim was to investigate whether NK cells, T-cells, NK T-like cells and invariant NK T-cells (iNK T-cells) are deficient in coeliac disease, Crohn’s disease and/or ulcerative colitis. Blood was collected for flow cytometry from normal control subjects, subjects with coeliac disease, Crohn’s disease and ulcerative colitis. The number of circulating NK cells, T-cells, NK T-like cells and iNK T-cells was assessed by three-colour flow cytometry. Intracellular cytokine production was measured after in vitro anti-CD3/ anti-CD28 antibodies, gluten fraction 3 and PMA:ionomycin stimulation. Vα24+ T-cells were quantified in ileocolonic biopsies by immunofluorescence and as mRNA by relative and real-time PCR (RT-PCR). The number of circulating Vα24+ T-cells and iNK T-cells decrease with age in normal healthy control subjects. Cytokine production was also affected by age. The work of this thesis has identified a subpopulation of otherwise normal healthy individuals whom have normal numbers of circulating Vα24+ T-cells, reduced numbers of circulating Vα24+ Vβ11+ T-cells and consequently iNK Tcells. Circulating CD161+ NK cells, Vα24+ T-cells and the SP subset of Vα24+ Tcells were reduced in coeliac disease. The low numbers of circulating Vα24+ T-cells was independent of diet. The number of circulating Vα24+ Vβ11+ Tcells were reduced in coeliac disease, and as a consequence, the number of circulating Vα24+ Vβ11+ α-GalCer/CD1d tetramer+ and Vα24+ 6B11+ iNK T-cells were reduced. The deficiency of Vα24+ T-cells was not confined to the blood, but observed within the intestinal mucosa. Intestinal Vα24 mRNA expression from subjects with coeliac disease was reduced compared to levels in normal subjects as assessed by relative and RT-PCR. Thus, Vα24+ T-cells were deficient in coeliac disease both systemically and mucosally. Cytokine production by Vα24+ T-cells, 6B11+ and Vα24+ α-GalCer/CD1d tetramer+ iNK T-cells after 4 h in vitro anti-CD3 stimulation was also impaired in subjects with coeliac disease. Circulating CD56+, CD57+, CD94+, CD161+ NK cells were reduced in Crohn’s disease and ulcerative colitis. Vα24+ T-cells and the SP subset of Vα24+ T-cells were reduced in Crohn’s disease but not in ulcerative colitis. Circulating Vα24+ Vβ11+ T-cells, Vα24+ Vβ11+ α-GalCer/CD1d tetramer+ and Vα24+ 6B11+ iNK T-cells were deficient in both Cohn’s disease and ulcerative colitis. The deficiency of Vα24+ T-cells was also observed within the intestinal mucosa. Intestinal Vα24 mRNA expression from Crohn’s disease and ulcerative colitis was reduced compared to levels in normal subjects as assessed by relative and RT-PCR. Cytokine production by Vα24+ T-cells, 6B11+ and Vα24+ α-GalCer/CD1d tetramer+ iNK T-cells after 4 h in vitro anti-CD3 stimulation was impaired for subjects with Crohn’s disease and ulcerative colitis. In summary, Vα24+ T-cell number and function were affected by age. Further investigations are warranted to see if deficiency of this immunoregulatory population is associated with disease. The decrease and dysfunction in immunoregulatory cells, Vα24 T-cells and iNK T-cells could contribute to the pathogenesis of coeliac disease, Crohn’s disease and ulcerative colitis. Coeliac disease, Crohn’s disease and ulcerative colitis are polygenetic diseases in which environmental factors play a significant role in disease development and state. The reduced numbers of iNK T-cell along with their impaired function may only be two factors. Presumably, other factors are involved. Nevertheless, iNK T-cells offer a potential target for the therapeutic intervention of coeliac disease, ulcerative colitis and Crohn’s disease. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345088 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2008