Sjogren's syndrome (SS) is a chronic, progressive autoimmune disease that most prominently affects the salivary and lacrimal glands. The disease can also produce systemic manifestations and is associated with systemic autoimmunity. The data are strong that SS is more common than any autoimmune rheumatic illness, except rheumatoid arthritis. The ultimate goal of the investigator's laboratory is to understand the mechanisms by which autoimmunity occurs and produces immune-mediated diseases such as SS. Immunizing with short peptides from 60 kD Ro, the PI has developed an animal model of SS that recapitulates not only the clinical and pathological manifestations including salivary gland lymphocytic infiltrate but also recapitulates the serologic manifestations including anti-Ro/SSA and anti-La/SSB. No other animal model of the disease reproduces the pathological and serological findings of human SS with such fidelity. In general, the PI hypothesizes that characterization of this animal model, which so closely mimics the human disease will lead to important insights into the genetics, and immunology of SS. In particular, the PI hypothesizes that the glandular infiltrates found in these animals will contain T and B lymphocytes with certain homing receptors and specificity for the Ro or La autoantigens. In the first specific aim this hypothesis will be tested by determining the phenotype and specificity of the lymphocytic infiltrate found in the salivary glands of the new animal model of Sjogren's syndrome.
In Specific Aim 2 the lymphocyte subset and the adhesion phenotype critical for the development of disease in the peptide-induced model of Sjogren's syndrome will be determined using an adoptive transfer model and taking advantage of selected genetically manipulated mice. In the third specific aim the PI will test the hypothesis that disease can be prevented with immature dendritic cell immunization. ? ? The work is important to public health because Sjogren's syndrome is a common disease but under diagnosed. The disease is poorly understood. Presently, the only available treatments are simply supportive and/or symptomatic. Improved understanding of the disease at a fundamental level is possible through study of animal models. Such understanding may lead to improved recognition and treatment. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017561-02
Application #
7269355
Study Section
Special Emphasis Panel (ZDE1-YL (33))
Program Officer
Shum, Lillian
Project Start
2006-08-01
Project End
2011-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$290,149
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Kurien, B T; Dsouza, A; Igoe, A et al. (2013) Immunization with 60 kD Ro peptide produces different stages of preclinical autoimmunity in a Sjögren's syndrome model among multiple strains of inbred mice. Clin Exp Immunol 173:67-75
Maier-Moore, Jacen S; Cañas, Carlos A; Tobón, Gabriel et al. (2013) The CCR5 delta 32 polymorphism (rs333) is not associated with Sjögren's syndrome or Type 1 Diabetes in Colombians. Clin Immunol 148:206-8
Kurien, Biji T; Dorri, Yaser; Bachmann, Michael et al. (2012) Induction of anti-Ro60/anti-La by immunisation with spectrin and induction of anti-spectrin by immunisation with Ro60 and 4-hydroxy-2-nonenal-modified Ro60 immunisation. Clin Exp Rheumatol 30:886-93
Kurien, Biji T; Porter, Andrew; Dorri, Yaser et al. (2011) Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren syndrome or systemic lupus erythematosus in BALB/c mice. Free Radic Biol Med 50:1222-33
Lee, Yun Jong; Scofield, Robert H; Hyon, Joon Young et al. (2010) Salivary chemokine levels in patients with primary Sjogren's syndrome. Rheumatology (Oxford) 49:1747-52
Kurien, Biji T (2009) Inhibition of p300 and nuclear factor-kappaB by curcumin and its role in diabetic nephropathy. Nutrition 25:973-4; author reply 975-6
Kurien, Biji T; Scofield, R Hal (2009) Bubbling hookah smoke through heat-solubilized curcumin/turmeric and incorporation of the curry spice as an additive or filter in cigarettes to minimize tobacco smoke-related toxicants. Med Hypotheses 73:462-3
Kurien, Biji T; Scofield, R Hal (2009) Oral administration of heat-solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals. Int J Cancer 125:1992-3