Recent advances in coeliac disease.

PURPOSE OF REVIEW: Worldwide awareness of coeliac disease in all ages continues to grow. This article aims to summarize critically the recent research advances in coeliac disease. RECENT FINDINGS: Large multicentre studies have provided further evidence of the role of environmental and nonhuman leucocyte antigen genetic factors in coeliac disease. Siblings of coeliac patients carry a high risk, but those found to have negative coeliac serology are very unlikely to develop the disease. Advances in the efficacy of serological antibody testing potentiate the possibility of future accurate screening programmes in the community. Adherence to a gluten-free diet remains paramount as the recognition of coeliac related complications increases. SUMMARY: Despite the encouraging progress that has taken place in our genetic and immunological knowledge of coeliac disease, early introduction of a gluten-free diet remains the cornerstone of treatment. Alternatives, however, aimed at altering the toxicity of cereal proteins are now looking more promising.

Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival.

AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS: In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro. By contrast, the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2(-/-) mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation.

Newly identified genetic risk variants for celiac disease related to the immune response.

Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.

Advances in coeliac disease.

PURPOSE OF REVIEW: The number of people diagnosed with coeliac disease continues to rise, and this article critically summarizes recent research into the condition. RECENT FINDINGS: Much work has been focused on clarifying the molecular pathways involving cytokines in coeliac disease. Such work will yield improved understanding of the complex pathogenesis of coeliac disease and novel therapeutic targets. SUMMARY: The recent literature predominantly focuses on both elucidating the pathogenesis and improving diagnostic strategies for coeliac disease, but further work into the treatment of coeliac disease is needed.

Advances in celiac disease.

PURPOSE OF REVIEW: Increasing numbers of atypical or asymptomatic cases of celiac disease are being diagnosed. This review aims to summarize recent critical research in celiac disease. RECENT FINDINGS: Alternative candidate genes outside of the human leukocyte antigen complex continue to be identified, whilst innate and adaptive immune responses to key gliadin epitopes are now both recognized to be important in celiac disease pathogenesis. SUMMARY: Serological tests and small bowel biopsy remain the cornerstones of diagnosis. Treatment options other than the restrictive gluten-free diet remain limited.

Gliadin, glutenin or both? The search for the Holy Grail in coeliac disease.

Wheat gluten was traditionally classified into gliadin and glutenin based upon solubility in aqueous alcohol. Gliadins were thought to be responsible for precipitating coeliac disease; glutenins were thought probably to be nontoxic. More recent classification, according to primary amino acid structure, reveals not only great heterogeneity but also similarities between different gliadin and glutenin proteins. Peptides derived from both groups are immunostimulatory in coeliac disease and it is highly probable that glutenin proteins are therefore toxic. Attempts to breed wheat with satisfactory baking properties tolerated by coeliac patients will be very difficult.

Advances in celiac disease.

PURPOSE OF REVIEW: This article primarily aims to review critically research in all aspects of celiac disease over the last year. As always, there has been a wealth of relevant papers. RECENT FINDINGS: The role of genetics in disease susceptibility is slowly becoming more clearly defined and a more detailed understanding of the disease processes at the molecular level is paving the way towards the development of specific targeted therapies. SUMMARY: Despite recent advances in our understanding of celiac disease, the gluten-free diet remains the only current viable therapy and even with advances in serological tests and markers, the duodenal biopsy remains the gold standard for diagnosis and monitoring of the response to therapy.

Advances in celiac disease.

PURPOSE OF REVIEW: The number of diagnoses of celiac disease, especially "silent" forms continues to rise world-wide. This review aims to summarize critically recent research in celiac disease. RECENT FINDINGS: New proteomic approaches with the development of a possible powerful animal model have potentially furthered the isolation of the epitopes within gliadin, and other related proteins, that are critical for the development of celiac disease. SUMMARY: The number of potential disease-triggering gliadin components remains large. Small bowel biopsies remain the gold-standard for both diagnosis and monitoring of treatment.

Cognitive dysfunction and health-related quality of life in long-term liver transplant survivors.

Although several studies have investigated short-term effects of liver transplantation on cognitive function and health-related quality of life, there have been no studies looking at long-term effects. Patients who received a single liver transplant at St James's University Hospital (Leeds, UK) before October 1, 1991, were invited to participate in this cross-sectional study. Cognitive function was assessed using the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, trail-making tests, the Stroop test, and the Benton Visual Retention Test. Anxiety and depression were documented using the Hospital Anxiety and Depression Scale. Health-related quality of life was assessed using the EuroQol. Twenty-five healthy volunteers acted as controls. Thirty-six patients had undergone transplantation before October 1, 1991. Thirteen patients (36%) had died, 6 patients had received more than one transplant, 2 patients did not speak English, and 3 patients did not want to participate, leaving 12 patients included in the study. Patients scored significantly lower on measures of health-related quality of life than healthy controls, but there were no differences in levels of anxiety or depression. Patients scored significantly lower than controls across a wide range of cognitive functions, suggesting global cognitive impairment. We show that patients who survive for more than 10 years after liver transplantation have significant cognitive dysfunction and poor health-related quality of life. Whether these patients never return to normal after transplantation or whether they experience an increased rate of decline in cognitive function and health-related quality of life is uncertain and requires further study.

New developments in celiac disease.

Celiac disease remains a challenge to the clinician and scientist. It is clearly more prevalent than was previously suspected. Much interest is seen in identifying the genetic factors, which predispose to disease and the environmental agents that can trigger it. Genome-wide searches have identified a number of chromosomal susceptibility loci. Specific gliadin epitopes are being analyzed. New diagnostic options include the tissue transglutaminase enzyme-linked immunosorbent assay. Neurologic disease and bone disease are intriguing complications of celiac disease and are gradually being defined.

Celiac disease.

Celiac disease is more prevalent than it was previously thought to be, and screening of selected population groups may reveal many new cases. Tissue transglutaminase appears to have a significant role in the degradation of gliadin and antigen production. Specific gliadin epitopes have been defined using T-cell responses. Bone disease is a significant problem for patients with celiac disease but management guidelines are being developed. Refractory sprue (nonresponsive celiac disease) appears to be a manifestation of enteropathy-associated T-cell lymphoma in most cases.