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Abstract Number: 2797

Identification of Serum Biomarker for the Glandular Dysfunction of Primary Sjögren’s Syndrome

Ayumi Nishikawa1, Katsuya Suzuki1, Yoshiaki Kassai2, Yuumi Gotou3, Takahiro Miyazaki4, Maiko Takiguchi4, Rimpei Morita5, Akihiko Yoshimura5 and Tsutomu Takeuchi1, 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Takeda Pharmaceutical Company, Fujisawa, Japan, 3Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Tokyo, Tokyo, Japan, 4Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Kanagawa, Japan, 5Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Biomarkers, proteomics and salivary hypofunction, Sjogren's syndrome

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Session Information

Date: Tuesday, November 10, 2015

Title: Sjögren's Syndrome: Translational Insights into Sjögren's Syndrome

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by dry eye and mouth. Measurements of un-stimulated salivary flow and Schirmer’s test are classically used as assessment of salivary and lachrymal gland dysfunction. However, these tests tend to be easily affected by environmental and psychological factors, and thus development of more stable and effective surrogate marker has been strongly desired for the objective evaluation in the clinical setting. In this study, we investigated novel serum protein biomarkers for the salivary dysfunction of pSS patients.

Methods: Serum protein concentrations were measured by comprehensive high throughput proteomics assay (SOMAscanTM). Candidate biomarkers positively correlated with glandular dysfunction of pSS patients were statistically analyzed. As objective indicators represents glandular dysfunction, uptake and excretion rate (%) of parotid gland (PG), submandibular gland (SMG) examined by 99m Tc schintigraphy and Greenspan’s grade score, and other clinical information were also applied to the study.

Results: A total of 1128 serum proteins in 30 pSS and 30 untreated rheumatoid arthritis (RA) patients, and 30 healthy controls were comprehensively screened using SOMAscanTM. We first screened differentially up- and down-regulated proteins among the three groups, 55 proteins were statistically extracted (p<0.05 in the U-test, and fold change ≥ 1.2 or ≤0.83). To then extract biomarker for the glandular dysfunction, the correlation between protein levels and data of schintigraphy or lip biopsy in pSS patients. Next, we calculated association 55 up-regulated proteins in pSS with intake and excretion rate. Finally, we identified that LAG3, TNF-R2, LKHA4, MMP-12, granzyme A, β2-microglobulin, HCG, PF-4 were negatively correlated with intake and excretion rate of salivary gland scintigraphy. Greenspan’s grade was positively correlated with β2-microglobulin, MCP-3, EPHB2, CCL28, and TRAIL-R4.

Conclusion: We successfully identified novel serum proteins associated with salivary dysfunction of pSS. These proteins may be potential therapeutic targets for salivary dysfunction.


Disclosure: A. Nishikawa, None; K. Suzuki, None; Y. Kassai, Takeda Pharmaceutical Company Limited, 3; Y. Gotou, Takeda Pharmaceutical Company Ltd, 3; T. Miyazaki, Takeda Pharmaceutical Company Ltd, 3; M. Takiguchi, Takeda Pharmaceutical Company Ltd, 3; R. Morita, None; A. Yoshimura, None; T. Takeuchi, Astellas Pharma Inc, Bristol-Myers KK, Chugai Pharmaceutical Co, Ltd, Daiichi Sankyo Co, Ltd, Eisai Co, Ltd, Mitsubishi Tanabe Pharma Corp, Pfizer Japan, Santen Pharmaceutical Co, Ltd, Takeda Pharmaceutical Co, Ltd, Teijin Pharma Ltd, AbbVie GK, Asahi Kas, 2,AbbVie GK, Bristol-Myers KK, Chugai Pharmaceutical Co, Ltd, Eisai Co, Ltd, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corp, Pfizer Japan Inc, Takeda Pharmaceutical Co, Ltd, Astellas Pharma Inc, and Daiichi Sankyo Co, Ltd; and consultant fees from, 8.

To cite this abstract in AMA style:

Nishikawa A, Suzuki K, Kassai Y, Gotou Y, Miyazaki T, Takiguchi M, Morita R, Yoshimura A, Takeuchi T. Identification of Serum Biomarker for the Glandular Dysfunction of Primary Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/identification-of-serum-biomarker-for-the-glandular-dysfunction-of-primary-sjogrens-syndrome/. Accessed .
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