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  • Jefferson Adams
    Jefferson Adams

    What's the Connection Between Seronegative Celiac Disease and Immunoglobulin Deficiency?

    Caption: Image: CC--Valerie Everett

    Celiac.com 11/04/2015 - A research team that conducted an analysis of the relationship between seronegative celiac disease and immunoglobulin deficiencies also conducted a literature search on the main medical databases, which revealed that seronegative celiac disease poses a diagnostic dilemma.

    Image: CC--Valerie EverettThe research team included F. Giorgio, M. Principi, G. Losurdo, D. Piscitelli, A. Iannone, M. Barone, A. Amoruso, E. Ierardi, and A. Di Leo. They are variously affiliated with the Section of Gastroenterology at University Hospital Policlinico, Department of Emergency and Organ Transplantation at University of Bari in Bari, Italy.

    They note that villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers in addressing seronegative celiac disease. They also note that immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of seronegative celiac disease patients may be useful.

    In the team's view, tTG-mRNA was similarly increased in seropositive celiac disease and suspected seronegative celiac disease, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders.

    An immune deregulation, severely lacking B-cell differentiatio, underlies the association of seronegative celiac disease with immunoglobulin deficiencies. Therefore, celiac disease may be linked to autoimmune disorders and immune deficits, known as common variable immunodeficiency (CVID)/IgA selective deficiency.

    CVID is a heterogeneous group of antibody dysfunction, whose association with celiac disease revealed only by a positive response to a gluten-free diet. The research team suggests a possible familial inheritance between celiac disease and CVID.

    Selective IgA deficiency, commonly associated with celiac disease, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare, with less than 300 documented cases, and is connected to celiac disease in 5% of cases.

    The team diagnosed seronegative celiac disease in a patient affected by sIgMD using the tTG-mRNA assay. One-year on a gluten-free diet restored IgM levels.

    This study data support a link between seronegative celiac disease and immunoglobulin deficiencies, and invites researchers to take a closer look at this connection.

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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, science, and advanced research, and scientific methods. He previously served as Health News Examiner for Examiner.com, and devised 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
    A team of Swiss researchers recently set out to examine the nature of T cell-mediated immuno-regulation in the gastrointestinal tract. The research team was made up of doctors L. Saurer and C. Mueller of the Institute of Pathology at the University of Bern in Switzerland.
    In the human intestinal tract, just a single layer of epithelial cells divides innate and adaptive immune effector cells from a wide array of antigens. Here, the immune system faces a tall task in accepting beneficial flora and dietary antigens while preventing the dissemination of potential pathogens. When the tightly controlled process of immune system reactions breaks down, harmful inflammation and damage may result.
    In light of this, a great deal of focus has shifted toward 'conventional' regulatory CD4+ T cells, including naturally occurring and adaptive CD4+ CD25+ Foxp3+ T cells, Th3 and Tr1 cells.
    However, control mechanisms in the intestinal mucosa are highly intricate, and include adaptations of non-haematopoietic cells and innate immune cells in addition to the presence of unconventional T cells with regulatory properties such as resident TCRγδ or TCRαβ CD8+ intraepithelial lymphocytes.
    In the study, L. Saurer and C. Mueller seek to provide an overview of the present body of knowledge on standard and non-standard regulatory T cell subsets (Tregs), with particular focus on clinical data and the potential role or malfunctioning of Tregs in four major human gastrointestinal diseases, i.e. inflammatory bowel diseases, celiac disease, food allergy and colorectal cancer.
    Their data confirms most of the findings derived from experimental animal models, and has implications for clinical immunology, food allergy, immunoregulation, immunotherapy, mucosal immunology, and regulatory T cell protocols. Their findings appear in the February 2009 issue of Allergy.



    Kristina Campbell
    Study Finds Gut Bacteria can Affect Intestines' Protective Layer
    Celiac.com 03/15/2011 - For celiacs, it's not really the cinnamon bun that's the enemy. Nor the pizza crust, nor the ravioli. It's the gliadin in these foods - the alcohol-soluble portion of the gluten protein - that's the real culprit.
    Gliadin is the "gladiator" of the human digestive tract. When we ingest gliadin, enzymes try to break it down into a form that can be absorbed by the small intestine. But gliadin resists, fighting hard to remain intact.
    A regular small intestine has, like any good fortress, a protective wall: the mucosal lining of the intestine. This layer of mucus normally acts as a barrier against gliadin's assaults. But in a celiac intestine, the mucosal lining is permeable. With gliadin's destructive power enhanced by its enzyme sidekick, tissue Transglutaminase (tTG), it quickly gets past this poorly-guarded layer.
    Scientists are working to put their finger on exactly what makes the mucosal lining of a celiac's small intestine so permeable.
    Now a January study by Czech researchers found at least one thing that affects the permeability of the intestinal mucosa: gut bacteria.
    In this study, called "Role of Intestinal Bacteria in Gliadin-Induced Changes in Intestinal Mucosa: Study in Germ-Free Rats", researchers tied off sections of rats' intestines and introduced various kinds of bacteria to each section. They wanted to measure the effect that these bacteria had on the intestinal mucus - or more specifically, on the goblet cells that produce the intestinal mucus. To ensure that the kinds of bacteria in the rats' intestines were under experimental control, the rats had been raised from birth in germ-free conditions.
    They found that introducing gliadin to the intestines had the effect of decreasing the mucus-producing cells, thereby eroding the intestines' protective layer. No big surprises there - gliadin is a fighter, a digestive "gladiator", after all.
    But when they added strains of so-called harmful bacteria, Escherichia coli (otherwise known as E coli) or Shigella, the mucus-producing cells decreased even more. The cells first secreted massive amounts of mucus, then promptly exhausted themselves and gave up. This left the intestine looking very similar to that of a person in the early stages of celiac disease, say the researchers.
    But the tale did indeed have a happy ending. Along came the good bacteria, Bifidobacterium bifidum (or "Biff" for short). The mucus-producing cells in the small intestine increased when Biff was present. In fact, Biff was able to partially reverse the mucus-decreasing effects of E coli and Shigella.
    The researchers concluded that the composition of gut bacteria has an effect on the protective mucus of the intestines: an overgrowth of bad bacteria decreases the protective layer, while the addition of good bacteria increases the protective layer. Their study may eventually lead to treatment options for human celiacs, by finding ways to protect tender intestines from the harmful effects of gliadin.
    Source:

    PLoS One. 2011 Jan 13;6(1):e16169

    Jefferson Adams
    Celiac.com 08/16/2012 - Tests for blood antibodies against native gliadin (anti-nGli) are still often assumed to perform better in the diagnosis of celiac disease in young children than tests for antibodies to deamidated gliadin (anti-dGli), tissue transglutaminase (anti-tTG), and endomysium (EmA).
    A team of researchers recently set out to determine whether testing IgG and IgA antibodies Against native gliadin was best for diagnosing celiac disease in children under 2-years old. Specifically they wanted to compare the performance of assays for anti-nGli, anti-dGli, anti-tTG, and EmA in this age group.
    The research team included T. Richter, X. Bossuyt, P. Vermeersch, H.H. Uhlig, M. Stern, A. Hauer, K.P. Zimmer, L. Mearin, J.H. Roo, C. Dähnrich, and T. Mothes.
    They are affiliated with the University Children's Hospital, the Children's Hospital of the Clinical Centre, "Sankt Georg," and the Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics at University Hospital in Leipzig, Germany; with the Department Laboratory Medicine of University Hospital in Leuven, Belgium, the University Children's Hospital in Tübingen, Germany, the University Children's Hospital in Graz, Austria, the University Children's Hospital in Giessen, Germany, the Department of Paediatrics at Leiden University Medical Centre in Leiden, The Netherlands, and with EUROIMMUN Medizinische Labordiagnostika GmbH in Lübeck, Germany.
    For their study, they conducted a retrospective analysis of 184 children. The study group included 42 children with celiac disease under normal diet, and a control group of 142 children up to 2 years of age.
    The team measured immunoglobulin (Ig) A- and IgG-anti-dGli, IgA- and IgG-anti-nGli, IgA- and IgG-anti-tTG, and IgA-EmA in blood samples. They calculated areas under receiver operating characteristics curves, sensitivities, specificities, positive and negative predictive values, positive and negative likelihood ratios, as well as diagnostic odds ratios.
    When all the data was complete, they found that only tests for IgG-anti-dGli, IgA-anti-tTG, and IgA-EmA had high specificity (≥0.96) connected with high sensitivity (≥0.86), with high positive predictive values (≥0.52 and ≥0.69 at pretest probabilities of 0.05 and 0.1, respectively) and negative predictive values (≥0.99 and ≥0.98 at pretest probabilities of 0.05 and 0.1, respectively).
    These tests also showed high positive likelihood ratio (≥24) at low negative likelihood ratio (≤0.15) and high diagnostic odds ratios (≥136).
    From their data, the team concluded that using anti-nGli tests to diagnose celiac disease in young children was not helpful. They maintain that IgA-anti-tTG, IgA-EmA, and IgG-anti-dGli provided much more reliable results than anti-nGli in diagnosing celiac disease in young children.
    Source:
    J Pediatr Gastroenterol Nutr. 2012 Jul;55(1):21-25.

    Jefferson Adams
    Blood Tests Different in Patients with Gluten Sensitivity Than in Those with Celiac Disease
    Celiac.com 12/03/2012 - Gluten sensitivity has recently been added to the spectrum of gluten-related disorders, but precise diagnostic markers do not yet exist. A research team recently set out to understand the blood test pattern of gluten sensitivity, and to compare it with the blood test pattern seen in celiac disease.
    The researchers included U. Volta, F. Tovoli, R. Cicola, C. Parisi, A. Fabbri, M. Piscaglia, E. Fiorini, G. Caio, of the Department of Clinical Medicine at University of Bologna's St. Orsola-Malpighi Hospital in Bologna, Italy.
    For their study, the researchers looked at blood samples from 78 patients with gluten-sensitivity and 80 patients with celiac disease. They assessed levels of immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA).
    They found positive readings for IgG AGA in 56.4% of patients with gluten-sensitivity, and in 81.2% of patients with celiac disease. Antibody levels for both groups were in the high range.
    They found IgA AGA in 7.7% of patients with gluten-sensitivity, and in 75% of patients with celiac disease, which shows lower enzyme-linked immunosorbent assay activities in gluten-sensitivity patients than in patients with celiac disease.
    Only 1 of the 78 patients with gluten-sensitivity tested positive for IgG DGP-AGA, which was found in nearly 90% of patients with celiac disease.
    All patients with gluten-sensitivity tested negative for IgA tTGA and IgA EmA, while 98.7% of patients with celiac disease tested positive for IgA tTGA, and 95% were positive for IgA EmA.
    Patients with gluten-sensitivity presented a variety of intestinal and extra-intestinal symptoms, including abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia. Small intestinal mucosa for these patients was either normal or only mildly abnormal.
    The data from these blood tests show that more than half of patients with gluten sensitivity will test positive for IgG AGA, and a small number will test positive for IgA AGA, but none will show positive results for EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
    Source:
    J Clin Gastroenterol. 2012 Sep;46(8):680-5.

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