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J Immunol. 2010 Apr 15;184(8):4236-46. doi: 10.4049/jimmunol.0902434. Epub 2010 Mar 17.

An autoimmune response to odorant binding protein 1a is associated with dry eye in the Aire-deficient mouse.

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  • 1Diabetes Center, University of California-San Francisco, San Francisco, CA 94143, USA.

Abstract

Sjögren's Syndrome (SS) is a human autoimmune disease characterized by immune-mediated destruction of the lacrimal and salivary glands. In this study, we show that the Aire-deficient mouse represents a new tool to investigate autoimmune dacryoadenitis and keratoconjunctivitis sicca, features of SS. Previous work in the Aire-deficient mouse suggested a role for alpha-fodrin, a ubiquitous Ag, in the disease process. Using an unbiased biochemical approach, however, we have identified a novel lacrimal gland autoantigen, odorant binding protein 1a, targeted by the autoimmune response. This novel autoantigen is expressed in the thymus in an Aire-dependent manner. The results from our study suggest that defects in central tolerance may contribute to SS and provide a new and clinically relevant model to investigate the pathogenic mechanisms in lacrimal gland autoimmunity and associated ocular surface sequelae.

PMID:
20237294
[PubMed - indexed for MEDLINE]
PMCID:
PMC2851482
Free PMC Article

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