Investigation of three potential autoantibodies in Sjogren’s syndrome and associated MALT lymphoma
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Li Cui1,2,3, Naseim Elzakra1,2, Shuaimei Xu4, Gary Guishan Xiao5, Yan Yang1,6, Shen Hu1,2
1UCLA School of Dentistry, Los Angeles, CA 90095, USA
2UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 900953, USA
3Department of Dentistry, Maoming People’s Hospital, Maoming 525000, China
4Guangdong Provincial Stomatological Hospital, Guangzhou 510000, China
5School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, 116024 China
6Department of Stomatology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Shen Hu, email: [email protected]
Yan Yang, email: [email protected]
Keywords: Rho GDP-dissociation inhibitor 2, alpha-enolase, cofilin-1, primary Sjögren’s syndrome, mucosal-associated lymphoid tissue lymphoma
Received: December 15, 2016 Accepted: January 24, 2017 Published: February 22, 2017
Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease which might progress to mucosal-associated lymphoid tissue lymphoma (pSS/MALT). Diagnosis of pSS requires an invasive tissue biopsy and a delay in diagnosis of pSS has been frequently reported. In this study, four proteins including cofilin-1, alpha-enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry, and the finding was verified by the microarray analysis and western blotting results. We then developed enzyme-linked immunosorbent assays for autoantibodies including anti-cofilin-1, anti-alpha-enolase and anti-RGI2 with good quantitative ability. The expression levels of salivary anti-cofilin-1, anti-alpha-enolase and anti-RGI2 were found to be the highest in pSS/MALT patients and lowest in healthy controls. The combination of these three antiantibodies yielded an “area under the curve” (AUC) value of 0.94 with an 86% sensitivity and 93% specificity in distinguishing patients with pSS from healthy controls, an AUC value of 0.99 with a 95% sensitivity and 94% specificity in distinguishing patients with pSS/MALT from healthy controls and an AUC value of 0.86 with a 75% sensitivity and 94% specificity in distinguishing pSS/MALT patients from pSS patients. Collectively, we have successfully identified a panel of potential autoantigens that are progressively up-regulated during the development of pSS and its progression to MALT lymphoma. The autoantibody biomarkers may be used to help diagnose pSS and predict its progression to MALT lymphoma.
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