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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AIRE Protein
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Animals
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Autoantibodies / biosynthesis*
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Autoantibodies / blood
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Dacryocystitis / genetics
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Dacryocystitis / immunology
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Dacryocystitis / pathology
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Disease Models, Animal
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Dry Eye Syndromes / genetics*
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Dry Eye Syndromes / immunology*
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Dry Eye Syndromes / pathology
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Female
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Humans
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Keratoconjunctivitis Sicca / genetics
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Keratoconjunctivitis Sicca / immunology
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Keratoconjunctivitis Sicca / pathology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred NOD
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Mice, Knockout
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Mice, Nude
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Mice, SCID
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Receptors, Odorant / biosynthesis
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Receptors, Odorant / genetics
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Receptors, Odorant / immunology*
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Sjogren's Syndrome / genetics*
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Sjogren's Syndrome / immunology*
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Sjogren's Syndrome / pathology
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Thymus Gland / pathology
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Transcription Factors / deficiency*
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Transcription Factors / genetics*
Substances
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Autoantibodies
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Receptors, Odorant
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Transcription Factors
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odorant-binding protein