Serum Clusterin and Complement Factor H May Be Biomarkers Differentiate Primary Sjögren's Syndrome With and Without Neuromyelitis Optica Spectrum Disorder.

Lin Qiao,Yongzhe Li,Yan Zhao,Yan Xu,Yunyun Fei,Qian Wang,Chuiwen Deng,Wen Zhang

doi:10.3389/fimmu.2019.02527

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a neurological complication of primary Sjögren's syndrome (pSS).Objective: We aimed to explore potential serological differences between pSS patients with and without NMOSD.Methods: There were 4 pSS patients with NMOSD and 8 pSS patients without NMOSD enrolled as the screening group for two-dimensional difference gel electrophoresis (DIGE) analysis. Then differential expressed protein spots between groups were identified by MALDI-TOF/TOF MS. The levels of the identified potential biomarkers were verified by ELISA in a second independent cohort including 22 pSS patients with NMOSD, 26 pSS without NMOSD and 30 NMOSD patients.Results: Nine proteins were identified significantly differently expressed (more than 1.5-fold, p < 0.05) between these two groups. Serum levels of clusterin and complement factor H (CFH) were further verified by ELISA. Results showed that the serum clusterin was significantly higher in NMOSD with pSS than without (298.33 ± 184.52 vs. 173.49 ± 63.03 ng/ml, p < 0.01), while the levels of CFH were lower in pSS patients with NMOSD than without (24.19 ± 1.79 vs. 25.87 ± 3.98 ng/ml, p < 0.01).Conclusion: This is the first study of serological comparative proteomics between pSS patients with and without NMOSD. Serum clusterin and CFH might be potential biomarkers for pSS patients with NMOSD and play important role in the pathogenesis of the disease but needs further verification.

Highlights

Primary Sjögren’s syndrome is a systemic autoimmune disease characterized by dry eyes and dry mouth
The symptoms of the central nervous system behave before mucosal symptoms and detection of anti-SSA/SSB antibody in Primary Sjögren’s syndrome (pSS) patients with neuromyelitis optica spectrum disorder (NMOSD) [9,10,11], which may result in ignoring the existence and treatment of pSS
The abundance of these protein spots was compared between pSS patients with and without NMOSD, and a total of 206 protein spots were found significantly differently expressed in the screening group

Summary

Introduction

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by dry eyes and dry mouth. About 40% of pSS patients were found to be complicated with neuromyelitis optica spectrum disorder (NMOSD) [1]. Early diagnosis and treatment of pSS patients with NMOSD will improve their prognosis. The diagnosis of pSS patients with NMOSD, especially NMOSD, was confronted with problems that the specific serum biomarker, anti-aquaporin (AQP4) antibody was not sensitive enough [7]. The similarity of sensitivity and specificity of AQP4 antibody in idiopathic NMOSD patients and NMOSD associated with autoimmune diseases is indicative of two distinct diseases with sequential or simultaneous incidences [8]. Neuromyelitis optica spectrum disorder (NMOSD) is a neurological complication of primary Sjögren’s syndrome (pSS)

Methods

Results

Conclusion