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    Is Epitope-Specific Immunotherapy for Celiac Disease a Foundation for Future Autoimmune Vaccines?


    Jefferson Adams
    Image Caption: Photo: CC--@alviseni

    Celiac.com 06/19/2013 - Currently, immunosuppressant drugs are the only real treatment option for most autoimmune disorders, such as celiac disease and Type 1 diabetes.


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    Photo: CC--@alviseniHowever, researchers are busily exploring the possibilities offered therapeutic vaccines, known as antigen-specific immunotherapy. ImmusanT is one company working to develop a vaccine that will allow patients with celiac disease to safely eat gluten (the antigen). That vaccine is presently undergoing clinical trials.

    ImmusanT and its research partners are looking to build on their expertise in celiac disease to improve their understanding of antigen-specific immunotherapy for other autoimmune diseases.

    In Current Opinion in Immunology, researchers Bob Anderson and Bana Jabri describe how identification of pathogenic T cell epitopes (segment of the antigen) and recent initiatives to optimize immune monitoring have helped drive rational vaccine design in human autoimmune diseases.

    Celiac disease has provided researchers with the first opportunity to design and test epitope-specific immunotherapy with a thorough understanding of disease-causing T cell epitopes.

    This approach offers "truly customized immunotherapy for patients with celiac disease according to their genetics and the molecular specificity of their immune response to gluten," said Bob Anderson, PhD, MBChB, Chief Scientific Officer of ImmusanT.

    Because celiac disease shares key features, such as susceptibility genes, presence of autoantibodies and destruction of specific cells, with other autoimmune disorders, like Type 1 diabetes and rheumatoid arthritis, it provides a model for understanding and exploring the triggers and drivers of autoimmunity, in general, write Drs. Bana Jabri and Ludvig Sollid in the Perspectives section in Nature Reviews Immunology.

    By factoring in the association with the major histocompatibility complex (MHC), post-translation modifications, the antigen and the tissue, researchers can design methods that help to the spot potential drivers of autoimmune disease.

    Because peptide-specific therapy specifically targets the immune cells that drive the disease process, "it offers the potential to prevent and cure disease, without inducing general immunosuppression," said Bana Jabri, MD, PhD, Director, University of Chicago Celiac Center; Professor, Department of Medicine, Pathology and Pediatrics, University of Chicago; and Senior Scientific Advisor to ImmusanT.

    Ludvig M. Sollid, MD, PhD, is Director, Centre for Immune Regulation; Professor of Medicine, Department of Immunology, University of Oslo; Consultant, Oslo University Hospital-Rikshospitalet; and member of ImmusanT's Scientific Advisory Board.

    Dr. Jabri is Co-Chair of the 15(th) International Celiac Disease Symposium to be hosted by the University of Chicago Celiac Disease Center, September 22-25, 2013.

    The event will draw the world's top scientists and physicians to discuss the most recent scientific advances in managing and treating celiac disease and gluten-related disorders.

     

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    Guest Melinda Jepson

    Posted

    This is good news for us gluten-free people.

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    Guest CeliacDiseaseCtr

    Posted

    Both of these doctors will be at the International Celiac Disease Symposium discussing their progress toward a cure... join us there, as the ICDS is a unique opportunity to have your questions answered about treating and curing gluten-related disorders!

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    Good news for GLUTEN-free persons and if it really works for the person. How long before it is ready to sell and how much will it cost?

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    Guest Ken Olson

    Posted

    Sounds interesting. What is the cost of the Symposium?

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    Guest Mark  Bogdany

    Posted

    Look forward to learning about more research like this!

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    By suppressing immune systems, I hope the body of celiac person would not susceptible to other diseases or the immune system would not malfunction.

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    Guest annaya

    Posted

    When will it be available???

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    Guest Rhonda

    Posted

    Good article. Even if the vaccine works, I will never knowingly eat gluten again. There is a reason it is so bad for us, and in general, all processed foods and GMOs are the real problem. However, it would be nice not to have the horrible results of inadvertently and unknowingly eating gluten.

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    Jefferson Adams
    Celiac.com 03/18/2010 - An international research team recently conducted an assessment of the nutritional status of children with newly diagnosed celiac disease, and compared the results to a group of matched control subjects.
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    Jefferson Adams
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    Source:

    Br J Nutr. 2009 Oct;102(8):1154-60.

    Jefferson Adams
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    Source:
    Nature. 2012 Mar 14;483(7389):345-9. doi: 10.1038/nature10863.

    Jefferson Adams
    Celiac.com 05/09/2014 - Even though we now have cheap, readily available celiac blood screening tests, more than eight out of every ten people with celiac disease remain undiagnosed, and the average time to in diagnosis of symptomatic individuals with celiac disease ranges from about six to eleven years.
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    Source:
    BMC Gastroenterology 2014, 14:42. doi:10.1186/1471-230X-14-42

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    Jefferson Adams
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    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
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    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

    Jefferson Adams
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    Ingredients:
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    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
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    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
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    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023