An autoimmune response to odorant binding protein 1a is associated with dry eye in the Aire-deficient mouse.
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.
DeVoss
Jason J
JJ
Diabetes Center, University of California-San Francisco, San Francisco, CA 94143, USA.
LeClair
Norbert P
NP
Hou
Yafei
Y
Grewal
Navdeep K
NK
Johannes
Kellsey P
KP
Lu
Wen
W
Yang
Ting
T
Meagher
Craig
C
Fong
Lawrence
L
Strauss
Erich C
EC
Anderson
Mark S
MS
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D003607:Dacryocystitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007638:Keratoconjunctivitis Sicca / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D018035:Receptors, Odorant / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics*; D000096927:AIRE Protein
D001323:Autoantibodies; D018035:Receptors, Odorant; D014157:Transcription Factors; D000096927:AIRE Protein; C045648:odorant-binding protein