| TACI-Fc gene therapy improves autoimmune sialadenitis but not salivary gland function in non-obese diabetic mice. | |
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MedLine Citation:
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PMID: 22212434 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Oral Diseases (2011) Objective: Patients with Sjögren's syndrome (SS) show aberrant expression of the B cell-related mediators, B cell-activating factor (BAFF), and a proliferation-inducing ligand (APRIL) in serum and salivary glands (SGs). We studied the biological effect of neutralizing these cytokines by local gene transfer of the common receptor transmembrane activator and CAML interactor (TACI) in an animal model of SS. Material and Methods: A recombinant serotype 2 adeno-associated virus (rAAV2) encoding TACI-Fc was constructed, and its efficacy was tested in the SGs of non-obese diabetic mice. Ten weeks later, SG inflammation was evaluated and serum and SG tissue were analyzed for inflammatory markers including immunoglobulins (Ig) and cytokines. Results: AAV2-TACI-Fc gene therapy significantly reduced the number of inflammatory foci in the SG, owing to a decrease in IgD(+) cells and CD138(+) cells. Moreover, IgG and IgM levels, but not IgA levels, were reduced in the SG. Overall expression of mainly proinflammatory cytokines tended to be lower in AAV2-TACI-Fc-treated mice. Salivary flow was unaffected. Conclusion: Although local expression of soluble TACI-Fc reduced inflammation and immunoglobulin levels in the SG, further research will have to prove whether dual blockade of APRIL and BAFF by TACI-Fc can provide a satisfying treatment for the clinical symptoms of patients. |
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Authors:
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Jl Vosters; N Roescher; Gg Illei; Ja Chiorini; Pp Tak |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-5 |
Journal Detail:
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Title: Oral diseases Volume: - ISSN: 1601-0825 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508565 Medline TA: Oral Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 John Wiley & Sons A/S. |
Affiliation:
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Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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