TACI-Fc gene therapy improves autoimmune sialadenitis but not salivary gland function in non-obese diabetic mice

Oral Dis. 2012 May;18(4):365-74. doi: 10.1111/j.1601-0825.2011.01885.x. Epub 2011 Dec 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / antagonists & inhibitors
  • B-Lymphocytes / pathology
  • Cytokines / analysis
  • Dependovirus / genetics
  • Disease Models, Animal
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Immunoglobulin A / analysis
  • Immunoglobulin D / analysis
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Inflammation Mediators / analysis
  • Ligands
  • Mice
  • Mice, Inbred NOD
  • Plasma Cells / pathology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / therapeutic use*
  • Saliva / chemistry
  • Saliva / metabolism
  • Secretory Rate / physiology
  • Sialadenitis / immunology
  • Sialadenitis / pathology
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / pathology
  • Sjogren's Syndrome / therapy*
  • Submandibular Gland / immunology
  • Submandibular Gland / metabolism
  • Submandibular Gland / pathology
  • Syndecan-1 / analysis
  • Transduction, Genetic
  • Transmembrane Activator and CAML Interactor Protein / genetics
  • Transmembrane Activator and CAML Interactor Protein / therapeutic use*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / antagonists & inhibitors


  • B-Cell Activating Factor
  • Cytokines
  • Immunoglobulin A
  • Immunoglobulin D
  • Immunoglobulin G
  • Immunoglobulin M
  • Inflammation Mediators
  • Ligands
  • Recombinant Fusion Proteins
  • Sdc1 protein, mouse
  • Syndecan-1
  • Tnfrsf13b protein, mouse
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • TACI receptor-IgG Fc fragment fusion protein