Natural history and pathogenesis of Sjogren's syndrome(SS) The primary objective of this study is to enable the collection of longitudinal clinical and laboratory data and biologic specimens to identify pathogenetic mechanisms of SS by careful clinical phenotyping of SS patients and Sjgrens-like conditions over time and collection of biologic samples for concurrent and future laboratory studies related to the pathogenesis of Sjgrens syndrome. Another objective of the study is to identify biomarker candidates associated with the diagnosis, severity, prognosis, or organ involvement in SS. Associated research projects: 1. Ex-vivo salivary gland functional imaging The molecular mechanisms underlying salivary gland secretory defects in SS is unknown. While the destruction of glandular structure can contribute to the decrease in total salivary fluid secretion, it does not explain the loss of secretion in patients who have low, or negligible, levels of inflammation in the glands (this group constitutes over 80% of the SS patients). By obtaining fresh minor salivary gland biopsies from SS patients and healthy volunteers, we examine single acinar cell function from intact acinar clusters, with confocal microscopy. We are able to measure calcium influx and release in individual cells and also measure individual cell volume changes after agonist stimulation. This has allowed us to focus on specific candidate proteins that might be responsible for the salivary gland dysfunction associated with SS 2.Trancriptome profiling of salivary glands There is an unmet need to characterize the molecular profile of the broad range of phenotypes in SS. With the advent of high throughput sequencing methods, a complete characterization of whole transcriptome of salivary glands and specifically of each of their resident cells types will greatly facilitate the sub-classification and better characterization of the genetic changes in SS patients. In SS the presence of different levels of inflammation in glands of patients present a challenge when whole glands are used as source of material. Under these circumstances, the analysis of genetic material and proteins from heterogeneous tissue sample as a whole, might mask the important changes that occur in the individual types of cells. Laser capture microdissection allows the procurement of specific cell types by dissecting out only cells of interest. We are planning to use parotid and minor salivary glands of SS patients and through laser capture microdissection isolate and characterize the genetic profile of ductal and acinar cells as well as the resident lymphocytes . Through this project proteins will also be isolated from each cell type and stored for future

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14
Fiscal Year
2015
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Dental & Craniofacial Research
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Billings, M; Amin Hadavand, M; Alevizos, I (2018) Comparative analysis of the 2016 ACR-EULAR and the 2002 AECG classification criteria for Sjögren's syndrome: Findings from the NIH cohort. Oral Dis 24:184-190
Billings, M; Dye, B A; Iafolla, T et al. (2017) Elucidating the role of hyposalivation and autoimmunity in oral candidiasis. Oral Dis 23:387-394
Corden, A; Handelman, B; Yin, H et al. (2017) Neutralizing antibodies against adeno-associated viruses in Sjögren's patients: implications for gene therapy. Gene Ther 24:241-244
Alevizos, I; Zheng, C; Cotrim, A P et al. (2017) Late responses to adenoviral-mediated transfer of the aquaporin-1 gene for radiation-induced salivary hypofunction. Gene Ther 24:176-186
Teos, Leyla Y; Alevizos, Ilias (2017) Genetics of Sjögren's syndrome. Clin Immunol 182:41-47
Alevizos, I; Zheng, C; Cotrim, A P et al. (2017) Immune reactivity after adenoviral-mediated aquaporin-1 cDNA transfer to human parotid glands. Oral Dis 23:337-346
Tandon, Mayank; Perez, Paola; Burbelo, Peter D et al. (2017) Laser microdissection coupled with RNA-seq reveal cell-type and disease-specific markers in the salivary gland of Sjögren's syndrome patients. Clin Exp Rheumatol :
Burbelo, Peter D; Gunti, Sreenivasulu; Keller, Jason M et al. (2017) Ultrarapid Measurement of Diagnostic Antibodies by Magnetic Capture of Immune Complexes. Sci Rep 7:3818
Gallo, Alessia; Jang, Shyh-Ing; Ong, Hwei Ling et al. (2016) Targeting the Ca(2+) Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjögren's Syndrome. EBioMedicine 10:216-26
Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao et al. (2016) Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells. J Biol Chem 291:8709-20

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