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Proteomic analysis of plasma from rheumatoid arthritis patients with mild cognitive impairment

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Abstract

Rheumatoid arthritis (RA) patients may suffer from comorbid neuropsychiatric symptoms including mild cognitive impairment (MCI). Although comorbidity of MCI is common, there are currently no validated plasma biomarkers to aid MCI diagnosis. This study screened plasma from patients with RA with and without comorbid MCI to identify potential biomarkers useful in the differential diagnosis of comorbid MCI. Plasma samples were collected from patients with RA without comorbid MCI, with comorbid MCI, and from healthy controls. Plasma samples were examined by tandem mass tags (TMT) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MSMS) to analyze protein expression. Differentially expressed proteins were identified by bioinformatics and validated by enzyme-linked immunosorbent assay (ELISA). A total of 746 reliable proteins and 158 differentially expressed proteins were identified. Fourteen patients with RA-MCI showed differential protein expression (six proteins upregulated and eight proteins downregulated) compared with those patients without MCI and with healthy controls. Bioinformatics analysis showed that the differentially expressed proteins were primarily involved in biological processes, such as cell adhesion, coagulation, apoptosis, and body fluid regulation. The results of the ELISA experiments, similar to those of the proteomic analysis, demonstrated that sonic hedgehog (SHH) was upregulated and serum paraoxonase (TTR) was downregulated in patients with RA-MCI. These results indicate that SHH and TTR may be candidate plasma biomarkers that could be used to distinguish patients with RA and comorbid MCI from those without comorbid MCI.

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Acknowledgements

We would like to thank Ya-Lan Zhang for help with the neuropsychological tests and Hong Wu and Qing-Xia You for their help collecting plasma samples. We also would like to thank Editage [www.editage.cn] for English language editing, and all the subjects and their families who agreed to participate in our research.

Funding

This study was supported by the General Program of National Natural Science Foundation of China (81373180).

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Author notes

  1. Li Yang and Qing-Hua Zou contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, First Affiliated Hospital of Third Military Medical University, Chongqing, 400038, China

    Li Yang, Qing-Hua Zou, Yin Shi, Cai-Xia Hui, Xiao-Fei Liu & Yong-Fei Fang

  2. Department of Psychosomatic Medicine, The Ninth People’s Hospital of Chongqing, Chongqing, China

    Yan Zhang & Chun-Rong Hu

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  1. Li Yang
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  3. Yan Zhang
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Correspondence to Yong-Fei Fang.

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The study was approved by the Ethics Committee of the First Affiliated Hospital of the Third Military Medical University and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All subjects gave their informed consent.

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Yang, L., Zou, QH., Zhang, Y. et al. Proteomic analysis of plasma from rheumatoid arthritis patients with mild cognitive impairment. Clin Rheumatol 37, 1773–1782 (2018). https://doi.org/10.1007/s10067-017-3974-1

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