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    Active Delivery of Recombinant Autoantigens via Genetically Modified Lactococcus Lactis Induces Ag-specific Tolerance


    Jefferson Adams

    Celiac.com 09/15/2009 - Active delivery of recombinant autoantigens or allergens to intestinal mucosa by genetically modified Lactococcus lactis (LL) offers a unique therapeutic approach for the induction of tolerance to gluten proteins.


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    A team of researchers recently set out to determine whether oral administration of LL-delivered DQ8-specific gliadin epitope induces Ag-specific tolerance.

    The research team was made up of Inge L. Huibregtse, Eric V. Marietta, Shadi Rashtak, Frits Koning, Pieter Rottiers, Chella S. David; Sander J. H. van Deventer, and Joseph A. Murray under the auspices of the Center for Experimental and Molecular Medicine of the Academic Medical Center of the University of Amsterdam in the Netherlands.

    Celiac disease is associated with either HLA-DQ2- or HLA-DQ8-restricted responses to specific antigenic epitopes of gliadin, and may be treated by induction of Ag-specific tolerance.

    The research team engineered LL to secrete a deamidated DQ8 gliadin epitope (LL-eDQ8d) and then observed the induction of Ag-specific tolerance in NOD AB degrees DQ8 transgenic mice. The team measured tolerance by delayed-type hypersensitivity reaction, cytokine measurements, eDQ8d-specific proliferation, and regulatory T cell analysis.

    Oral administration of LL-eDQ8d induced suppression of local and systemic DQ8-restricted T cell responses in NOD AB degrees DQ8 transgenic mice. Result was an Ag-specific decrease of the proliferative capacity of inguinal lymph node (ILN) cells and lamina propria cells. Production of IL-10 and TGF-beta and a significant induction of Foxp3(+) regulatory T cells were associated with the eDQ8d-specific suppression induced by LL-eDQ8d.

    These results support the development of orally administered Ag-secreting LL to treat gluten-sensitive disorders. Such treatments may be effective even in cases of established hypersensitivity.


    Journal of immunology (Baltimore, Md. : 1950) 2009;183(4):2390-6

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    This is really encouraging! I wonder how soon it will be tested in humans?

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    Jefferson Adams
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    Jefferson Adams
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    Source:

    Sci Transl Med 21 July 2010: Vol. 2, Issue 41, p. 41ra51


    Jefferson Adams
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    J Clin Gastroenterol. 2012 Jan;46(1):46-50.

    Jefferson Adams
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    Source:
     Clin Exp Immunol. 2009 Oct;158(1):106-14. doi: 10.1111/j.1365-2249.2009.03999.x.

  • Recent Articles

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    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
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    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023

    Jefferson Adams
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    Source:
    Alimentary Pharmacology & Therapeutics

    Jefferson Adams
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    Source:
    Gut. 2017 Feb;66(2):250-257. &nbsp;doi: 10.1136/gutjnl-2015-310148.