Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis

Souto-Carneiro, Margarida; Tóth, L; Behnisch, Rouven; Urbach, Konstantin; Klika, Karel D.; Carvalho, Rui A.; Lorenz, Hanns‐Martin

doi:10.1136/annrheumdis-2019-216374

Cited by 77 publications

(93 citation statements)

References 51 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, oxylipin profiling led us to identify differences between seronegative and seropositive RA. Although previous metabolomics studies have shown distinct metabolomic signatures in seronegative RA patients, the exact compounds have not been elucidated (49). Our results confirm that whereas both subsets could be distinguished from controls based on oxylipin signatures, the precursors and pathways greatly differed between them.…”

Section: Discussionsupporting

confidence: 76%

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Rodríguez‐Carrio

Coras

Alperi-López

et al. 2021

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes. Methods. In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry. Results. Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified. Conclusion. Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.

show abstract

Section: Discussionsupporting

confidence: 76%

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Rodríguez‐Carrio

Coras

Alperi-López

et al. 2021

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…For starters, the use of well-accepted standardized food intake surveys in future metabolomics studies may give a handle on this variable. ► The above recommendations apply not only to metabolomics studies in SLE, but also to similar investigations in other rheumatic diseases such as rheumatoid arthritis and primary Sjögren’s syndrome, where these same confounding factors have been consistently overlooked [ 65 – 72 ]. …”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

Caution in studying and interpreting the lupus metabolome

Zhang

Mohan

2020

Arthritis Res Ther

View full text Add to dashboard Cite

Several metabolomics studies have shed substantial light on the pathophysiological pathways underlying multiple diseases including systemic lupus erythematosus (SLE). This review takes stock of our current understanding of this field. We compare, collate, and investigate the metabolites in SLE patients and healthy volunteers, as gleaned from published metabolomics studies on SLE. In the surveyed primary reports, serum or plasma samples from SLE patients and healthy controls were assayed using mass spectrometry or nuclear magnetic resonance spectroscopy, and metabolites differentiating SLE from controls were identified. Collectively, the circulating metabolome in SLE is characterized by reduced energy substrates from glycolysis, Krebs cycle, fatty acid β oxidation, and glucogenic and ketogenic amino acid metabolism; enhanced activity of the urea cycle; decreased long-chain fatty acids; increased medium-chain and free fatty acids; and augmented peroxidation and inflammation. However, these findings should be interpreted with caution because several of the same metabolic pathways are also significantly influenced by the medications commonly used in SLE patients, common co-morbidities, and other factors including smoking and diet. In particular, whereas the metabolic alterations relating to inflammation, oxidative stress, lipid peroxidation, and glutathione generation do not appear to be steroid-dependent, the other metabolic changes may in part be influenced by steroids. To conclude, metabolomics studies of SLE and other rheumatic diseases ought to factor in the potential contributions of confounders such as medications, co-morbidities, smoking, and diet.

show abstract

“…Our RA patients with US at synovitis, most of them RF and ACPA-, showed lower levels of serum biomarkers, resembling PsA patients [30]. Therefore, sero-RA could represent a different entity, standing between sero + RA and PsA, as it has also been suggested in recent studies analyzing serum metabolomes and lipidomes [31].…”

Section: Discussionmentioning

confidence: 72%

Proliferative Synovitis, an Ultrasound Pattern Associated with ACPA positive Patients, Erosive Disease and Enhanced Need to Change Therapy in Rheumatoid Arthritis

Ramírez¹,

Azuaga-Piñango²,

Frade‐Sosa³

et al. 2020

Preprint

View full text Add to dashboard Cite

Objectives: To analyze ultrasound (US) differences between rheumatoid arthritis (RA) patients according to their autoantibody status and characterize the clinical, immunological and radiological features associated with the US pattern of seropositive patients.Methods: We collected clinical and immunological data along with bilateral hand US images of RA patients. Serum biomarkers, MRI of dominant hand and immunostaining of synovial biopsies were performed.Results: Two hundred and five RA patients were collected (84.8% seropositive). No significant differences in disease activity/therapy were found according to autoantibodies status. An extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal that we called US Proliferative Synovitis (US PS) was present in 55.5% of seropositive and 16.1% of seronegative patients, (p=0.0001). In the multivariate analysis, erosions [OR 4.90 CI 95% (2.17-11.07). p=0.0001] and ACPA [OR 3.5 CI 95% (1.39-10.7), p=0.09] but not RF status [OR 0.74 CI 95% (0.31-1.71), p=0.483] were independently associated with the presence of US PS. Ninety-four per cent of joints with US PS scored 2-3 in RAMRIS synovitis sub-index. At synovial level, US PS was significantly associated with higher density of vessels (p=0.042). Moreover, significantly higher serum levels of angiogenic and inflammatory cytokines were found in patients with US PS. After a mean of 46 months of follow-up, US PS was independently associated with change of therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016).Conclusions: ACPA+ RA was associated with US PS. This US pattern significantly detected erosive disease and an enhanced need to change therapy in the long-term.

show abstract

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis

Cited by 77 publications

References 51 publications

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Caution in studying and interpreting the lupus metabolome

Proliferative Synovitis, an Ultrasound Pattern Associated with ACPA positive Patients, Erosive Disease and Enhanced Need to Change Therapy in Rheumatoid Arthritis

Contact Info

Product

Resources

About