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Hello all! I'm fairly new to this community. Although I've been reading many posts on here for a while, this is only my second posting! I am pre-diagnosis, although I am almost 100% certain that I am at least gluten sensitive. Due to time, I'll make another post later on detailing more of my symptoms and my experiences on this crazy journey. Currently on a gluten-free diet because it is not worth the suffering (cheated enough times that now just looking at a cookie makes my everything hurt). This question is more towards anybody who has a good understanding of genes, alleles, etc. I have finally coughed up the dough to get genetic testing done, and my alleles are HLA-DQ 8 and HLA-DQ 3. To my very elementary understanding, HLA-DQ 8 is one of the two HLA genes associated with the development of celiac disease. There is also some controversial and currently unreplicated data suggesting that HLA-DQ 3 is associated with gluten sensitivity. Regardless of that controversial piece, it is also my understanding that HLA-DQ 8 is a "form" of the HLA-3 allele. If HLA-DQ 8 is a form of HLA-DQ 3, what is the difference between HLA-DQ 3 and HLA-DQ 8, that I have both of them? In other words, what makes it HLA-DQ 3, instead of one of its sub-categories or forms? Not sure if the question makes sense, or if anybody knows! Thanks for any info!!
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.com 01/22/2018 - Celiac disease is marked by HLA-DQ2/8-restricted responses of CD4+ T cells to gluten from wheat, barley or rye. Currently, in order to properly diagnose celiac disease based on serology and duodenal histology doctors need patients to be on gluten-containing diets. This is a problem for many people, who prefer not to begin ingesting wheat again once they have adopted a gluten-free diet. This can present challenges for doctors attempting to diagnose celiac disease. It is known that HLA-DQ–gluten tetramers can be used to detect gluten-specific T cells in the blood of patients with celiac disease, even if they are on a gluten-free diet. The team set out to determine if an HLA-DQ–gluten tetramer-based assay can accurately identify patients with celiac disease. The research team included Vikas K. Sarna, Knut E.A. Lundin, Lars Mørkrid, Shuo-Wang Qiao, Ludvig M. Sollid, and Asbjørn Christophersen. They are variously affiliated with the Department of Immunology, Oslo University Hospital – Rikshospitalet, Norway; the KG Jebsen Coeliac Disease Research Centre, University of Oslo, Norway; the Department of Gastroenterology, Oslo University Hospital – Rikshospitalet, Norway; the Department of Medical Biochemistry, Oslo University Hospital – Rikshospitalet, Norway; and with the Centre for Immune Regulation, Oslo University Hospital – Rikshospitalet and University of Oslo, Norway. For their study, the team produced HLA-DQ–gluten tetramers and added them to peripheral blood mononuclear cells isolated from 143 HLA-DQ2.5+ subjects. There were a total of 62 subjects with celiac disease on a gluten-free diet, 19 subjects without celiac disease on a gluten-free diet due to perceived sensitivity, 10 subjects with celiac disease on a non-gluten-free diet, and 52 seemingly healthy individuals as control subjects. The team used flow cytometry to measure T cells that bound HLA-DQ–gluten tetramers. They then used researchers blinded to sample type, except for samples from subjects with celiac disease on a gluten-containing diet, to conduct laboratory tests and flow cytometry gating analyses. They also conducted analysis on test precision using samples from 10 subjects. They found that an HLA-DQ–gluten tetramer-based test that detects gluten-reactive T cells identifies patients with and without celiac disease with a high level of accuracy, regardless of whether patients are on a gluten-free diet. This test could conceivably allow celiac diagnosis while suspected patients are still on a gluten-free diet. The team notes that their results require a larger study for validation. Could reliable celiac diagnosis be done without making patients consume gluten? Will that become common? Stay tuned for more developments. Source: Gastrojournal.org
Jefferson Adams posted an article in Celiac Disease Diagnosis, Testing & TreatmentCeliac.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)