Dataset Information

Human Rheumatoid Arthritis LC-MSMS

ABSTRACT: Malondialdehyde-modified epitopes (MDA-epitopes) can elicit specific autoantibody that expressed oxidative stress arising in rheumatoid arthritis (RA). The purpose of this study was to discover and validate MDA-peptide adducts as novel biomarkers using concanavalin A affinity chromatography, 1D SDS-PAGE, in-gel digestion, and label-free nano-LC-MS, and evaluate levels of serum MDA, MDA-protein adducts, proteins and autoantibody isotypes against an unmodified and MDA-peptide from Taiwanese female patients with RA and healthy controls (HCs). Levels of serum MDA and MDA-protein adducts were significantly higher in RA patients versus HCs. Four differentially expressed novel MDA-peptides were selected that relative modification ratio were 2-fold differences to examine protein levels and assess autoantibodies to MDA-peptides in RA patients compared with HCs. Four of peptides are autoantigens. Furthermore, 4 MDA-peptides can induce more autoantibody isotypes that are statistical significance in RA patients compared to HCs. Serum IgG and IgM against MDA-peptides showed excellent diagnostic performance in discriminating among RA patients and HCs: area under the curve (AUC, 0.96 ~ 0.98), sensitivity (88.9% ~ 97.8%) and specificity (88.9% ~ 100%). Autoantibodies to MDA-epitopes indicate oxidative modifications occurring in RA, and might be useful as clinical markers fro RA diagnosis if further investigated.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Ching-Yu Lin

LAB HEAD: Ching-Yu Lin

PROVIDER: PXD004546 | Pride | 2021-02-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	F0705-TMU-Lin-RA-ConA-1-1.mgf	Mgf
	F0705-TMU-Lin-RA-ConA-1-1.pride.mgf.gz	Mgf
	F0705-TMU-Lin-RA-ConA-1-2.mgf	Mgf
	F0705-TMU-Lin-RA-ConA-1-2.pride.mgf.gz	Mgf
	F0705-TMU-Lin-RA-ConA-1-3.mgf	Mgf

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Publications

Isotypes of autoantibodies against novel differential 4-hydroxy-2-nonenal-modified peptide adducts in serum is associated with rheumatoid arthritis in Taiwanese women.

Tsai Kai-Leun KL Chang Che-Chang CC Chang Yu-Sheng YS Lu Yi-Ying YY Tsai I-Jung IJ Chen Jin-Hua JH Lin Sheng-Hong SH Tai Chih-Chun CC Lin Yi-Fang YF Chang Hui-Wen HW Lin Ching-Yu CY Su Emily Chia-Yu EC

BMC medical informatics and decision making 20210210 1

<h4>Background</h4>Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients.<h4>Methods</h4>Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Fo ...[more]

PMID: 33568149

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Project description:Background: Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. Methods: We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ≥ 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the ‘high risk autoantibody profile (HRP)’ as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines/chemokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. Results: In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1b in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p=0.04) and a 26% lower IL-1b (p=0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p=0.0006, p=0.006, p=0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations. Conclusions: Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity may occur systemically, rather than at the joint, which may provide insight into the systemic effects of RA-related autoantibodies and inflammation in the absence of clinically apparent RA.