Investigation of three potential autoantibodies in Sjogren's syndrome and associated MALT lymphoma

// Li Cui 1, 2, 3 , Naseim Elzakra 1, 2 , Shuaimei Xu 4 , Gary Guishan Xiao 5 , Yan Yang 1, 6 , Shen Hu 1, 2 1 UCLA School of Dentistry, Los Angeles, CA 90095, USA 2 UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 900953, USA 3 Department of Dentistry, Maoming People’s Hospital, Maoming 525000, China 4 Guangdong Provincial Stomatological Hospital, Guangzhou 510000, China 5 School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, 116024 China 6 Department of Stomatology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China Correspondence to: Shen Hu, email: shenhu@ucla.edu Yan Yang, email: yanyangwhu@yahoo.com 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 ABSTRACT 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.