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  • Jefferson Adams
    Jefferson Adams
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    Can Science Take the Guesswork Out of Diagnosing Seronegative Celiac Disease?

      Can science improve current diagnosis of seronegative celiac disease?

    Caption: Can science bring any certainty to diagnosing seronegative celiac disease? Photo: CC--Saturnism

    Celiac.com 09/27/2017 - Patients who have clinical, genetic and histological signs of celiac disease, but no serological markers, present a challenge when it comes to making a diagnosis. If the patient doesn't have elevated antibodies, what signs do doctors look for? What's the best way to evaluate the patient's natural history and response to a gluten-free diet?

    A team of researchers recently set out to outline a specific profile, and to evaluate the natural history and response to a gluten-free diet of patients with seronegative celiac disease.

    The research team included Maria Pina Dore; Giovanni Mario Pes; Ivana Dettori; Vincenzo Villanacci; Alessandra Manca and Giuseppe Realdi. They are variously affiliated with the Internal Medicine Section, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy, with the Baylor College of Medicine, Michael E. DeBakey VAMC, Houston, TX, USA, the Pathology Section, Department of Molecular and Translational Medicine, Spedali Civili and University of Brescia, Brescia, Italy, and with the Pathology Section, Department of Clinical and Experimental Medicine, University of Sassari in Sassari, Italy.

    Patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of celiac disease, but with negative celiac serology, were defined as seronegative celiac patients.

    The team excluded other common causes of duodenal mucosa damage. They the compared HLA–DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive celiac disease. They then assessed clinical features, lab tests and histological findings after a gluten-free diet and a gluten re-challenge. The group provided the team with a long follow-up period to gather data.

    The researchers enrolled a total of 48 patients who fulfilled diagnostic criteria over a 4-year period. Patients with seronegative and seropositive celiac disease showed similar clinical phenotype and HLA−DR and DQ frequencies. However, Marsh I stage was seen in 42% of seronegative patients (42% vs 22%; p<0.05).

    After a 1-year gluten-free diet trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative celiac disease (25%) experienced the occurrence of autoimmune diseases during an average follow-up of about 11 years.

    Patients with seronegative celiac disease did not show any specific profile, but they did see benefits from a gluten-free diet similar to seropositive patients.

    In the absence of more sensitive serological markers, diagnosing seronegative celiac disease remains an often confusing and challenging process of excluding various other possibilities.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Can Antibodies Spot Celiac Disease in Kids Without a Biopsy?
    Celiac.com 06/05/2017 - Doctors diagnose celiac disease by confirming various clinical, genetic, serologic, and duodenal morphology features. Based on retrospective data, recent pediatric guidelines propose eliminating biopsy for patients with IgA-TTG levels more than 10-times the upper limit of normal (ULN), along with a few other criteria.
    One retrospective study showed that researchers using levels of IgA-TTG and total IgA, or IgA-TTG and IgG against deamidated gliadin (IgG-DGL) could identify patients both with and without celiac disease. A team of researchers recently set out to validate the positive and negative predictive values (PPV and NPV) of these diagnostic procedures.
    The research team included Johannes Wolf, David Petroff, Thomas Richter, Marcus KH. Auth, Holm H. Uhlig, Martin W. Laass, Peter Lauenstein, Andreas Krahl, Norman Händel, Jan de Laffolie, Almuthe C. Hauer, Thomas Kehler, Gunter Flemming, Frank Schmidt, Astor Rodriques, Dirk Hasenclever, and Thomas Mothes.
    Their team conducted a prospective study of 898 children undergoing duodenal biopsy analysis to confirm or rule out celiac disease at 13 centers in Europe. They then compared results from antibody tests with results from biopsies, follow-up data, and diagnoses made by the pediatric gastroenterologists. In all cases, diagnosis was made for celiac disease, no celiac disease, or no final diagnosis.
    Blinded researchers measured levels of IgA-TTG, IgG-DGL, and endomysium antibodies, while tissue sections were analyzed by local and blinded reference pathologists. The team validated two procedures for diagnosis: total-IgA and IgA-TTG, as well as IgG-DGL with IgA-TTG. Patients whose antibody concentrations for all tests were below 1-fold the ULN were assigned to the no celiac disease category.
    Those whose antibody concentrations for at least one test were above 10-fold the ULN were assigned to the celiac disease category. All other cases were considered to require biopsy analysis.
    The team calculated the ULN values using the cut-off levels suggested by the test kit manufacturers. They conducted HLA-typing for 449 participants. To extrapolate the PPV and NPV to populations with lower rates of celiac disease, they used models that accounted for how specificity values change with prevalence.
    In all, the team found 592 patients with celiac disease, 345 who did not have celiac disease, and 24 with no final diagnosis.
    The TTG-IgA procedure identified celiac disease patients with a PPV of 0.988 and an NPV of 0.934. The TTG-DGL procedure identified celiac disease patients with a PPV of 0.988 and an NPV of 0.958.
    Their extrapolation model estimated that PPV and NPV would remain above 0.95 even at a disease prevalence as low as 4%. Meanwhile, tests for endomysium antibodies and HLA type did not increase the PPV of samples with levels of IgA-TTG 10-fold or more above the ULN.
    Interestingly, the pathologists disagreed in their analyses of duodenal morphology about 4.2% of the time, a rate comparable to the error rate for serologic tests.
    This study validates the use of the TTG-IgA procedure and the TTG-DGL procedure in lieu of biopsy to diagnose pediatric patients with or without celiac disease.
    Source:
    Gastroenterology. DOI: http://dx.doi.org/10.1053/j.gastro.2017.04.023  
    The researchers are variously affiliated with the Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Medical Faculty of the University and University Hospital, Leipzig, Germany, the Institute for Medical Informatics, Statistics & Epidemiology (IMISE), University of Leipzig, Germany, the Department of Paediatrics, University of Oxford, Oxford, United Kingdom, the Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom, the, University Children's Hospital Halle, Germany, the Medical School, Hannover, Germany, Helios Hospital, Department of Paediatrics, Plauen, Germany, the Children's Hospital Prinzessin Margaret, Darmstadt, Germany, the University Children's Hospital Graz, Austria, the Children's Hospital, Justus Liebig University Giessen, Germany, the University Children's Hospital Leipzig, Germany, the Children's Hospital of the Clinical Centre Sankt Georg Leipzig, Germany, the Clinical Trial Centre, University of Leipzig, Germany, the DKD Helios Children's Hospital, German Clinic for Diagnostics, Wiesbaden, Germany, the University Children's Hospital, Technical University Dresden, Germany, and the Alder Hey Children's National Health Service Foundation Trust, Liverpool, United Kingdom.

    Jefferson Adams
    Do We Really Need Biopsies to Diagnose Celiac Disease?
    Celiac.com 07/13/2017 - Until recently, duodenal biopsy was considered the gold standard for diagnosing celiac disease, but that is changing.
    A number of studies have shown that celiac disease can be diagnosed using serological tests alone, but many clinicians have yet to embrace this approach.
    In both retrospective and prospective studies, one research team showed that certain IgA-tissue transglutaminase antibodies levels can predict celiac disease in adults 100% of the time.
    After making some adjustments to the analytical method for measuring the antibody, a team of researchers recently set out to to determine whether such serum tests can reliably diagnose celiac disease in large numbers adult patients without the need for small bowel biopsy.
    The research team included GKT Holmes, JM Forsyth, S Knowles, H Seddon, PG Hill, and AS Austin.
    They are variously associated with the Royal Derby Hospital, the Department of Pathology, and the Derby Digestive Diseases Centre at the Royal Derby Hospital in Derby, UK.
    For their study, the team conducted a retrospective analysis in an unselected series of 270 adult patients who underwent small bowel biopsies and the measurement of serum IgA-tissue transglutaminase antibody levels from 2009 to 2014.
    At an IgA-tissue transglutaminase antibody cut-off greater than 45 U/ml (>8×upper limit of normal+2SDs) the positive predictive value for celiac disease in this cohort was 100%; 40% of cases were above this cut-off.
    The team found that they could use IgA-tissue transglutaminase antibody levels to reliably diagnose celiac disease in a high proportion of these adult patients.
    This study adds to the growing body of evidence that supports the diagnosis of celiac disease without a mandatory small bowel biopsy.
    As a realist of these findings, the study team has changed the diagnostic guidelines for their center, and will now make celiac diagnosis based on cut-off levels of IgA-tissue transglutaminase.
    This is exciting news. For many, many years, the biopsy was considered the gold standard for diagnosing celiac disease.
    By eliminating biopsies in favor of IgA-tissue transglutaminase levels, diagnosing celiac disease could become much easier and even cheaper.
    Do you have celiac disease? Did you receive a biopsy for diagnosis? How do you feel about celiac diagnosis without biopsy? Share your thoughts below.
    Source:
    Eur J Gastroenterol Hepatol. 2017 Jun;29(6):640-645. doi: 10.1097/MEG.0000000000000841.

    Jefferson Adams
    Will New Tests and Devices Change Celiac Diagnostics and Management?
    Celiac.com 09/11/2017 - The FDA has granted clearance for Immco Diagnostics' ELISA for celiac disease, and for Roche's Benchtop Analyzer. What does that mean?
    Immco's test is conducted as a solid phase immunoassay and is intended for the qualitative or semiquantitative detection of IgA or IgG antigliadin antibodies in human blood, and thus to aid in diagnosing patients with celiac disease or dermatitis herpetiformis in conjunction with other laboratory and clinical findings.
    In other important diagnostic news, a benchtop analyzer from Roche Diagnostics and an immunoassay system from Shenzhen New Industries Biomedical was among the instruments and tests cleared by the US Food and Drug Administration in July, according to the agency. The FDA granted 510(k) clearance to Roche's Cobas b 101 instrument platform, as well as the Cobas HbA1c test. The fully automated and self-contained Cobas b 101 uses a single-use reagent disc to measure HbA1c from capillary and/or venous whole-blood samples, according to a document filed with the FDA.
    The Cobas HbA1c is an in vitro diagnostic test for detecting the presence of glycate hemoglobin, which develops when hemoglobin joins with glucose in the blood, becoming 'glycated'. By measuring glycated hemoglobin (HbA1c), clinicians are able to get an overall picture of what our average blood sugar levels have been over a period of weeks/months.
    For people with diabetes this is important as the higher the HbA1c, the greater the risk of developing diabetes-related complications. The HbA1c assay is designed for use with the Cobas b 101 platform, which is not a portable home test, but is intended for a clinical laboratory or point-of-care setting.
    Other instruments receiving FDA clearance in July include a new flow cytometer from Becton Dickinson; an expanded version of Bruker's MALDI Biotyper; and expanded indications for BioMérieux's Vitek MS MALDI-TOF Mass Spectrometery System. The FDA recently cleared the Maglumi 2000 automated immunoassay analyzer from Shenzhen New Industries Biomedical, which uses chemiluminescent technology for running IVD tests on clinical serum samples. The firm's Maglumi 2000 TSH assay for the quantitative determination of thyroid-stimulating hormone in human serum also received 510(k) clearance. The assay is for diagnosing thyroid disorders.
    These are just a few of many new tests and analysis devices that are changing the way doctors diagnose and manage celiac disease, diabetes, and other diseases.
    Look for tests like this to have a profound influence on the way diseases are diagnosed and managed in the future.
    Read more: 360dx.com

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    Got the result today, and it is indeed the IgG only, and it is "negative" with a result of: <10.0 Units I have sent a message to my doctor requesting that she at least also order the TTG IGA test. However, I'm assuming that this result does at least significantly lower the likelihood that I have celiac? This is all just a shot in the dark anyhow... but after 8 years of unsatisfactorily diagnosed mystery joint pain, I don't want to only half-explore an option and then abandon it without a reasonably definitive result.
    It sounds like you were not given the full celiac panel. The full celiac panel includes: TTG IGA
    TTG IGG
    DGP IGA
    DGP IGG
    EMA
    IGA You have to be eating gluten daily for 12 weeks before the blood test. A positive on any one blood test should lead to a gastroenterologist doing an endoscopy /biopsies to confirm a celiac diagnosis.    
    Yep, dang just realized I had a $10 off code in my email for the coffee you could have used. Yeah I love the coffees, some are odd. Most dessert ones require you to sweeten to bring it out, some you only taste cold. They are fun to play with and I love how they give me enjoyment when it comes to food.
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