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. 2024 Jul:147:103260.
doi: 10.1016/j.jaut.2024.103260. Epub 2024 May 25.

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue

Julia E Manning  1 , Emma Harris  2 , Hannah Mathieson  3 , Louise Sorensen  4 , Raashid Luqmani  5 , Helen M McGettrick  6 , Ann W Morgan  7 , Stephen P Young  8 , Sarah L Mackie  9
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Free article

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue

Julia E Manning et al. J Autoimmun. 2024 Jul.
Free article

Abstract

Objective: In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA).

Methods: Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms.

Results: The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R2 > 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R2 = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R2 = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R2 ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R2 > 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change).

Conclusion: PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.

Keywords: Fatigue; Giant cell arteritis; Glucocorticoid; Metabolomics; Polymyalgia rheumatica.

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Conflict of interest statement

Declaration of competing interest SLM has conducted consultancy on behalf of her institution for Roche/Chugai, Sanofi, AstraZeneca, AbbVie and Pfizer; was supported by Roche to attend EULAR 2019 and by Pfizer to register for virtual attendance at ACR2021. AWM has received research funding from Roche and has conducted consultancy on behalf of her institution for Roche/Chugai, Sanofi, Regeneron, GlaxoSmithKline, AstraZeneca and Vifor. JEM and HMM have received research funding from Novartis. HMM has received funding from Roche and Pfizer. RL has received funding from Celgene, Pfizer, Roche and Vifor. Other authors have no competing interests to declare.

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