Hans Olav Ueland, Arve Ulvik, Kristian Løvås, Anette S B Wolff, Lars Ertesvåg Breivik, Ann-Elin Meling Stokland, Eyvind Rødahl, Roy Miodini Nilsen, Eystein Husebye, Grethe Åstrøm Ueland
The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 6, June 2023, Pages 1290–1297
https://doi.org/10.1210/clinem/dgad004
Graves disease (GD) is one of the most common autoimmune disorders. Recent literature has shown an immune response involving several different inflammatory related proteins in these patients.
This work aimed to characterize the kynurenine pathway, activated during interferon-γ (IFN-γ)–mediated inflammation and cellular (T-helper type 1 [Th1] type) immunity, in GD patients with and without thyroid eye disease (TED).
We analyzed 34 biomarkers by mass spectrometry in serum samples from 100 patients with GD (36 with TED) and 100 matched healthy controls. The analytes included 10 metabolites and 3 indices from the kynurenine pathway, 6 microbiota-derived metabolites, 10 B-vitamers, and 5 serum proteins reflecting inflammation and kidney function.
GD patients showed significantly elevated levels of 7 biomarkers compared with healthy controls (omega squared [ω2] > 0.06; P < .01). Of these 7, the 6 biomarkers with the strongest effect size were all components of the kynurenine pathway. Factor analysis showed that biomarkers related to cellular immunity and the Th1 responses (3-hydroxykynurenine, kynurenine, and quinolinic acid with the highest loading) were most strongly associated with GD. Further, a factor mainly reflecting acute phase response (C-reactive protein and serum amyloid A) showed weaker association with GD by factor analysis. There were no differences in biomarker levels between GD patients with and without TED.
This study supports activation of IFN-γ inflammation and Th1 cellular immunity in GD, but also a contribution of acute-phase reactants. Our finding of no difference in systemic activation of the kynurenine pathway in GD patients with and without TED implies that the local Th1 immune response in the orbit is not reflected systemically.
We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.