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Dig Dis Sci 1999;44:2344-2349. Celiac.com 04/10/2000 - Dr. Carme Farre, of Hospital Sant Joan de Deu, in Barcelona, Spain, and his multi-center colleagues, report in the November issue of Digestive Diseases and Sciences that both serologic markers and the human lymphocyte antigen class II extended DQ2 (HLA-DQ2) haplotype are useful markers for screening first-degree relatives of patients with celiac disease for the disorder. These markers are more reliable predictors of celiac disease than other clinical features, which are absent from one third of relatives of people with celiac disease. The researchers examined the usefulness of serologic markers, HLA-DQ2 haplotype, and clinical features common to celiac disease in the diagnosis of the disorder in 675 first-degree relatives of celiac disease patients. The diagnosis was confirmed by intestinal biopsy. Their results showed that 5.5% of the subjects were diagnosed with celiac disease, which is significantly higher than what was observed in the general public in a previous study. Serum IgA-class anti-endomysium antibodies (IgA-AEA) and IgA-class anti-gliadin antibodies (IgA-AGA) were observed in 5.8% and 1.9% of the relatives, respectively. According to the researchers: Our results show that IgA-AEA is the most useful marker, since all but one IgA-AEA-positive relative showed histological findings of [celiac disease]. Further, the measurement of IgA-AGA would have missed 66% of the affected relatives. The researchers also concluded that the HLA-DQ2 haplotype also appeared to be a more useful indicator to determine which first-degree relatives had an increased genetic susceptibility to celiac disease, because the marker was detected in 93% of first-degree relatives found to have celiac disease, and 18% of those without it. The four most common clinical symptoms for celiac disease, diarrhea, anemia, food intolerance and growth retardation, were not found in one third of the relatives of patients with celiac disease. The researchers conclude: Although the definitive diagnosis of [celiac disease] relies upon the intestinal biopsy, it should be preceded by a noninvasive, inexpensive and easy-to-perform screening technique. Their findings indicate that using blood serum IgA-AEA measurements is a useful screening tool for noninvasive screening, and HLA-DQ2 assessment may delineate a very high risk population with a particular genetic susceptibility to [celiac disease].
Celiac.com 10/15/2014 - A team of researchers recently set out to assess the benefits of a gluten-free diet for people whose blood screens show markers for celiac disease, but who show no physical symptoms. Specifically, they investigated whether screen-detected and apparently asymptomatic adults with endomysial antibodies (EmA) benefit from a gluten-free diet. The research team included K. Kurppa, A. Paavola, P. Collin, H. Sievänen, K. Laurila, H. Huhtala, P. Saavalainen, M. Mäki, and K. Kaukinen. They are variously associated with the Tampere Center for Child Health Research, the Tampere School of Health Sciences of the University of Tampere and Tampere University Hospital, the Department of Gastroenterology and Alimentary Tract Surgery at Tampere University Hospital and School of Medicine, University of Tampere, the UKK Institute in Tampere, Finland, the Research Program Unit of the Immunobiology and Haartman Institute at the Department of Medical Genetics of the University of Helsinki in Helsinki, Finland, and the Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland and Seinäjoki Central Hospital, Seinäjoki, Finland. For their study, they conducted a prospective trial of 3031 individuals at risk for celiac disease based on screens for EmA. They found 40 of 148 seropositive individuals who fulfilled inclusion criteria. They randomly assigned the 40 patients to groups receiving either a gluten-free diet, or a gluten-containing diet. They then evaluated ratios of small-bowel mucosal villous height:crypt depth, serology and laboratory test results, gastrointestinal symptom scores, physiologic well-being, perception of health by a visual analog scale, bone mineral density, and body composition at baseline and after 1 year. From that point on, they switched the group on the gluten-containing diet to a gluten-free diet, evaluated them a third time. Patients in the first gluten-free diet group remained on that diet. After 1 year on the gluten-free diet, the mean mucosal villous height:crypt depth values increased (P < .001), levels of celiac-associated antibodies decreased (P < .003), and gastrointestinal symptoms improved compared to patients on gluten-containing diets (P = .003). The gluten-free diet group showed less indigestion (P = .006), reflux (P = .05), and anxiety (P = .025), and better overall health, based on the visual analog scale (P = .017), compared gluten-containing diet group. Only social function scores improved more in the gluten-containing diet group than in the gluten-free diet group (P = .031). There were no differences between groups in terms of lab test results, bone mineral density, or body composition. Most measured parameters improved when patients in the gluten-containing diet group were placed on gluten-free diets. No subjects considered their experience to be negative and most expected to continue eating gluten-free. The results show that a gluten-free diet benefits asymptomatic EmA-positive patients, and show the benefits of actively screening patients at risk for celiac disease. Source: Gastroenterology. 2014 Sep;147(3):610-617.e1. doi: 10.1053/j.gastro.2014.05.003.
Celiac.com 09/28/2007 - Figures concerning the diagnostic accuracy of various serologic test and HLA-DQ typing for diagnosing celiac disease have largely come from case–control studies. A team of doctors recently set out to assess the performance of serologic testing and HLA-DQ typing in the diagnosis of celiac disease. Results of their study were published recently in the Annals of Internal Medicine. The team was made up of Muhammed Hadithi, MD; B. Mary E. von Blomberg, PhD; J. Bart A. Crusius, PhD; Elisabeth Bloemena, MD, PhD; Pieter J. Kostense, PhD; Jos W.R. Meijer, MD, PhD; Chris J.J. Mulder, MD, PhD; Coen D.A. Stehouwer, MD, PhD; and Amado S. Peña, MD, PhD Their study looked at patients who had been referred for small bowel biopsy to determine weather they had celiac disease, and evaluated the effectiveness of serologic testing for celiac disease, specifically of antigliadin antibodies (AGA), antitransglutaminase antibodies (TGA), and anti-endomysium antibodies (EMA) and HLA-DQ typing. Data was measured by comparing the performance of serologic testing and HLA-DQ against a reference baseline of abnormal histologic findings and clinical resolution after a gluten-free diet. Of 463 participants, sixteen had celiac disease (prevalence = 3.46% [95% CI, 1.99% to 5.55%]). Testing positive on both TGA and EMA showed a corresponding sensitivity of 81% (CI, 54% to 95.9%), specificity of 99.3% (CI, 98.0% to 99.9%), and negative predictive value of 99.3% (CI, 98.0% to 99.9%). A positive test for either HLA-DQ type increased both sensitivity (100% [CI, 79% to 100%]) and negative predictive value (100% [CI, 98.6% to 100%]), while testing negative for both minimized the negative likelihood ratio (0.00 [CI, 0.00 to 0.40]) and post-test probability (0% [CI, 0% to 1.4%]). Adding HLA-DQ typing to TGA and EMA testing, and adding serologic testing to HLA-DQ typing, saw no corresponding difference in test performance compared with either testing strategy alone. Overall results show TGA and EMA testing were the most sensitive serum antibody tests and a negative HLA-DQ type excluded the celiac disease from the diagnosis. However, the addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, provided no change of test performance compared with either form of testing alone. Finally, the findings were somewhat limited, as low number of overall cases of celiac disease rule out meaningful comparisons of testing strategies. Annals of Internal Medicine (volume 147, pages 294-302)