Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

Sung Won Kwon,Mina Kim,Youngjae Park,Sang Jun Yoon,Hyun-Sook Kim,Wan-Uk Kim,Johan Lim,Seonghun Cho,Jung Hee Koh

doi:10.1038/s12276-022-00725-z

Abstract

Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.

Highlights

A better understanding of the pathogenesis of rheumatoid arthritis (RA) has led to a marked improvement in patient management over the past three decades; inexorable joint destruction and disability have become infrequent, and sustained remission is a realistic target of treatment[1,2,3]
Lipidome profiles in the synovial fluid of RA patients are altered significantly To investigate the effect of inflammation on the lipidome profile, SF samples from patients with RA (RA-SF) were analyzed as two separate groups: samples with a white blood cell (WBC) count
We identified 205 synovial lipidomes belonging to 13 lipid subclasses; we conducted one-way analysis of variance (ANOVA) followed by Tukey’s honestly significant difference (HSD) test to identify significant differences in lipidome expression among these groups (Table 1)

Summary

Introduction

A better understanding of the pathogenesis of rheumatoid arthritis (RA) has led to a marked improvement in patient management over the past three decades; inexorable joint destruction and disability have become infrequent, and sustained remission is a realistic target of treatment[1,2,3]. Early diagnosis and early initiation of disease modifying anti-rheumatic drug (DMARD) therapy are key components of the treatment strategy, the definition of ‘early RA’ is not clear. It refers to the initial phase, when arthritis is detected clinically[4]. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are autoantibodies representative of RA; these antibodies precede the clinical manifestations of RA by a median of 4.5 years[5]. To date, these two autoantibodies are the only available biomarkers for early RA6,7. Approximately half of patients with positive RF and/or ACPA do not develop RA5,8

Methods

Results

Conclusion