Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis
Authors: Tae-Hwan Kim
Kwang Pyo Kim
Jong-Seo Kim
Jinseol Rhee
Ji-Hyun Lee
Won-Ki Baek
Jae Hun Jung
Chang-Nam Son
Sang-Hyon Kim
Jeesoo Kim
Journal: Clinical Proteomics (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ankylosing spondylitis; Biomarker; Proteomics; Synovial fluid.
Affiliations: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keimyung University, Daegu, South Korea., Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin, South Korea., Center for RNA Research, Institute of Basic Science (IBS), Seoul, 08826 South Korea., School of Biological Sciences, Seoul National University, Seoul, 08826 South Korea., Department of Microbiology, School of Medicine, Keimyung University, Daegu, South Korea., New Drug R&D Center, ARIBIO Co. Ltd., Seongnam, South Korea., Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Abstract:  Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS. Methods: A cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC-MS/MS results were verified by western blotting. Results: We identified 8 proteins that were &gt; 1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting. Conclusion: We performed quantitative comparative proteomic analysis using by LC-MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease. 

Retracted: No

PubPeer comments:
 This review article contains no less than 906 references. A natural question arises, are the authors sufficiently familiar with each of these 906 sources so that they are ready to cite them? What happens if one of these sources proves unreliable? As a one-case example, I am very interested how deeply the authors looked into the reference 762, which is (762) Thilagaraj, M.; Arunkumar, N.; Ramkumar, S.; Hariharasitaraman, S. Electrooculogram Signal Identification for Elderly Disabled Using Elman Network. Microprocess. Microsyst. 2021, 82, 103811. ,