Jump to content
  • Join Our Community!

    Do you have questions about celiac disease or the gluten-free diet?

  • Jefferson Adams
    Jefferson Adams

    Immunohistochemical and T-Cell Receptor Gene Rearrangement Can Help Determine Morbidity and Mortality in Refractory Celiac Disease

    Caption: Photo: CC--IceSabre

    Celiac.com 04/24/2013 - Doctors classify refractory celiac disease (RCD) depending on the presence or absence of monoclonal expansions of intraepithelial lymphocytes (IELs) with an aberrant immunophenotype.

    Photo: CC--IceSabreA team of researchers recently set out to determine whether IEL parameters have any connection with mortality and morbidity in cases of refractory celiac disease.

    The research team included C. Arguelles-Grande, P. Brar, P. H. Green, and G. Bhagat. They are variously affiliated with the Celiac Disease Center, and the Departments of Medicine, Pathology and Cell Biology, at Columbia University Medical Center in New York, NY.

    The team used immunohistochemistry to assess IEL phenotype and polymerase chain reaction to determine T-cell receptor (TCR) gene rearrangement in 67 patients with RCD type I, and six patients with RCD type II. They considered a monoclonal TCR gene rearrangement and presence of greater than 50% CD3 CD8 IELs to be abnormal.

    They used Kaplan-Meier and Cox proportional hazard analyses to determine the time to worsening of clinical symptoms and the predictors of worsening. The team found 30 patients with less than 50% CD3 CD8 IELs, and eight with monoclonal TCR rearrangements. Three patients died and 40 suffered clinical worsening despite treatment.

    Estimated 5-year survival rates were 100% in patients with greater than 50% CD3 CD8 IELs and polyclonal TCR, but just 88% in patients with less than 50% CD3 CD8 IELs and 50% in patients with monoclonal TCR.

    All patients with monoclonal TCR gene rearrangement with less than 50% CD3 CD8 IELs showed shorter average time to clinical worsening of symptoms (11 mo), when compared to patients with less than 50% CD3 CD8 IELs alone (21 mo), polyclonal TCR (38 mo), or greater than 50% CD3 CD8 IELs alone (66 mo).

    After the team adjusted for age and gender, they found that the presence of less than 50% CD3 CD8 IELs was the only factor associated with increased risk for clinical worsening, despite negative celiac blood screens (hazard ratio=4.879; 95% confidence interval, 1.785-13.336; P=0.002).

    This means that RCD patients with <50% CD3 CD8 IELs are at risk for clinical worsening, and that RCD patients who also show monoclonal TCR gene rearrangement have higher mortality rates.

    Overall, the assessment of IEL phenotype and TCR gene rearrangement can provide important information regarding morbidity and risk of death in cases of RCD.

    Source:


    User Feedback

    Recommended Comments

    There are no comments to display.



    Join the conversation

    You can post now and register later. If you have an account, sign in now to post with your account.
    Note: Your post will require moderator approval before it will be visible.

    Guest
    Add a comment...

    ×   Pasted as rich text.   Paste as plain text instead

      Only 75 emoji are allowed.

    ×   Your link has been automatically embedded.   Display as a link instead

    ×   Your previous content has been restored.   Clear editor

    ×   You cannot paste images directly. Upload or insert images from URL.


  • 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

    Destiny Stone
    Celiac.com 08/18/2010 - The importance of an accurate celiac disease diagnosis is becoming increasinglymore evident to health practitioners and the general public worldwide. While the outcomes of undiagnosed celiac disease are still unclear,current  studies are attempting to find an answer.
    Between 1995 and 2001, serum samples were obtained from 16,886 Olmsted County, Minnesota citizens 50 years of age or older with unknown celiac status.
    Out of 16,847 adults studied, 129 cases were discovered to have undiagnosed celiac disease. 127 undiagnosed celiacs and 254 unmatched controls were then submitted for a systematic evaluation in search of over 100 possibly coexisting ailments.
    The scientists found that while celiac disease has been associated with an elevated risk for cancer, this study found no significant risk increase for cancer in undiagnosed celiacs compared to the control group.
    Researchers also found that those patients with undiagnosed celiac disease displayed an increased rate of osteoporosis and hypothyroidism. Furthermore, undiagnosed celiacs were also found to typically have a lower body mass index, and lower levels of ferritin and cholesterol, and to be less prone to arthritis and have a reduced rate of glucose intolerance. The correlation between lower arthritis and glucose intolerance in undiagnosed celiacs is speculated to be a result of a lower body mass index. 
    In conclusion, researchers were not able to determine a connection between undiagnosed celiac in older adults and comorbidity. In fact, except for impaired bone health, most undiagnosed celiacs in this study displayed little comorbidity and they did not have increased mortality rates when compared to the control group.
    Researchers of this study therefore concluded that there may be advantages and disadvantages to being an older undiagnosed celiac.
    Source:

    Gastroentrology doi:10.1053/j.gastro.2010.05.041

    Jefferson Adams
    Celiac.com 06/20/2014 - Celiac disease is a T cell–mediated disease triggered by the protein in wheat gluten. More than 9 out of 10 of people with celiac disease carry human leukocyte antigen (HLA)-DQ2 locus.
    A team of researchers recently set out to determine if T-cell receptor recognition of HLA-DQ2–gliadin complexes was connected with celiac disease.
    The researchers included Jan Petersen, Veronica Montserrat, Jorge R Mujico, Khai Lee Loh, Dennis X Beringer, Menno van Lummel, Allan Thompson, M Luisa Mearin, Joachim Schweizer, Yvonne Kooy-Winkelaar, Jeroen van Bergen, Jan W Drijfhout, Wan-Ting Kan, Nicole L La Gruta, Robert P Anderson, Hugh H Reid, Frits Koning, and Jamie Ross.
    They are variously affiliated with the Department of Biochemistry and Molecular Biology at the School of Biomedical Sciences, and the Australian Research Council Centre of Excellence in Advanced Molecular Imaging at Monash University in Clayton, Victoria, Australia, the Department of Pediatrics, and the Department of Immunohematology and Blood Transfusion at Leiden University Medical Center in Leiden, The Netherlands, the Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, at the University of Melbourne in Parkville, Victoria, Australia, ImmusanT, Inc., in Cambridge, Massachusetts, USA, and the Institute of Infection and Immunity at Cardiff University School of Medicine in Heath Park, Cardiff, UK.
    The team first determined T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epitopes from wheat gliadin, DQ2.5-glia-α1a and DQ2.5-glia-α2.
    They also determined the ternary structures of four distinct biased TCRs specific for those epitopes. They were able to establish a basis for the biased TCR usage through mutagenesis and affinity measurements, together with the fact that all three TCRs specific for DQ2.5-glia-α2 docked centrally above HLA-DQ2. They found that a non–germline–encoded arginine residue within the CDR3β loop served as key of this common docking footprint.
    Although the TCRs specific for DQ2.5-glia-α1a and DQ2.5-glia-α2 docked similarly, their interactions with the respective gliadin determinants differed markedly, thereby providing a basis for epitope specificity.
    This is the first time a research team has determined that T-cell receptor recognition of HLA-DQ2–gliadin complexes was connected with celiac disease. Further study is needed to better understand the nature of their relationship.
    Source:
    NATURE STRUCTURAL & MOLECULAR BIOLOGY

×
×
  • Create New...