ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 515

Stages of Sjogren’s Syndrome Defined by Immune Mediators

Lakshmanan Suresh1, Julian Ambrus Jr.2 and Long Shen3, 1Laboratory Medicine, IMMCO Diagnostics Inc., Amherst, NY, 2Division of Allergy, Immunology and Rheumatology, Department of Medicine, State University of New York at Buffalo, Buffalo, NY, 3Department of Medicine, SUNY at Buffalo, Buffalo, NY

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Sjögren's Syndrome - Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Sjogren’s syndrome (SS) is characterized by destruction of the salivary and lachrymal glands but also systemic manifestations such as lung disease, kidney disease and lymphomas. We have utilized an animal model for SS, the IL-14alpha transgenic mouse (IL14aTG; J. Immunol. 177: 5676 – 5686, 2006; Clin. Immunol. 130: 304-312, 2009) to understand factors regulating various aspects of the disease. Previous studies had demonstrated that IL14aTG mice lacking lymphotoxin did not develop any features of SS (IL14aTG.LTa-/-; J. Immunol. 185: 6355 – 6363, 2010).

Methods:

IL-14aTG mice lacking the type 1 interferon receptor  (IL14aTG.IFNR-/-) or marginal zone B cells (MZB; IL14aTG.CD19Cre.RBP-J-/-) were compared to IL14aTG mice with regards to autoantibodies (determined by Western blots), salivary gland secretions (determined after Pilocarpine stimulation), and histology of the salivary glands.

Results:

Both IL14aTG mice and IL14aTG.IFNR-/- developed IgM autoantibodies at 6 months, but only IL14aTG mice developed IgG antibodies at 12 months of age. IgM antibodies were eliminated in IL14aTG.CD19Cre.RBP-J-/- at 6 months of age. Salivary gland secretions were normal in IL14aTG.LTa-/- and IL14aTG.CD19Cre.RBP-J-/- mice, mildly decreased in IL14aTG.IFNR-/- and severely decreased in IL14aTG mice at 12 months of age. Both IL14aTG and IL14aTG.IFNR-/-mice had lymphocytic infiltration of their submandibular and lachrymal glands at 10 months of age. Only IL14aTG mice had lymphocytic infiltration of the parotid glands at 14 months of age. Neither IL14aTG.LTa-/- nor IL14aTG.CD19Cre.RBP-J-/- had lymphocytic infiltration of any salivary or lachrymal glands.

Conclusion:

These studies suggest a model for SS in which early injury to the submandibular and lachrymal glands is regulated by MZB that produce IgM antibodies and lymphotoxin. Later development of IgG autoantibodies and parotid gland injury is dependent upon type 1 interferon. Further studies will be needed to investigate these observations in patients with SS.

Disclosure:

L. Suresh,
None;

J. Ambrus Jr.,
None;

L. Shen,
None.

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