Sphingolipid Levels in RA Serum Samples May Affect RA Pathophysiology

Rheumatoid arthritis x-ray of the right hand.
Elevated levels of certain serum sphingolipids collected from patients with rheumatoid arthritis (RA) suggest that they may play an important role in RA pathophysiology.

Elevated levels of certain serum sphingolipids collected from patients with rheumatoid arthritis (RA) suggest that they may play an important role in RA pathophysiology, according to results published in Rheumatology.

Using serum samples, researchers sought to determine if sphingolipids could serve as biomarkers in patients with RA. Serum samples were collected from 82 participants. Participant age, gender, age of disease onset, disease duration, Disease Activity Scores in 28 Joints (DAS-28), rheumatoid factor, anti-citrullinated protein antibodies, human leukocyte antigen B27, and ongoing treatment information were also noted.

Participants were divided into 5 groups: Patients with untreated early RA (<1-year disease duration; n=18), patients with established active RA (>1 year after disease onset, DAS-28 >3.2, receiving treatment with conventional disease-modifying antirheumatic drugs and corticoids; n=19), patients with untreated early arthritis who did not meet RA classification criteria (<1 year after disease onset; n=13), patients with established active spondyloarthritis (SpA) with peripheral symptoms (>1 year after disease onset, treatment with nonsteroidal anti-inflammatory drugs; n=12), and healthy controls (n=20).

Increased levels of sphingosine (So), monohexosylceramide (HexCer), and ceramide (Cer) were identified in patients with established RA compared with controls. The most significant of these was So (coefficient value 0.106), followed by HexCer (coefficient value 0.077). Patients with early RA also showed a significant increase in So levels compared with controls (coefficient value 0.043). Conversely, patients in the established SpA group showed decreased levels of Cer compared with patients in the control group (coefficient value -0.091).

When investigators controlled for conventional disease-modifying antirheumatic drugs and corticoid therapies, the increase in So remained significant in patients with early RA, but was lost after Bonferroni correction (coefficient value 0.043). Among patients with established RA, levels of HexCer remained significantly increased when compared with control patients (coefficient value 0.347), while Cer levels were significantly lower in patients with SpA compared with controls (coefficient value -0.093).

A second model demonstrated that age and corticoid therapy were negatively associated with HexCer; however, none of these findings remained after Bonferroni correction. No significant difference was detected between the first and second measurements of each lipid in any model.

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“We could detect significantly higher levels of sphingolipids (most notably HexCer) in the serum of established RA patients as compared with controls,” the researchers concluded. “This elevation is consistent with the known roles of sphingolipids in inflammation.”

They added, “[T]he significance of serum sphingolipids as clinically useful biomarkers for RA remains unproven and its possible relationship with the cytokine environment of the different phases of the disease still has to be clarified.”


Miltenberger-Miltenyi G, Cruz-Machado AR, Saville J, et al. Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients [published online December 6, 2019]. Rheumatology. doi: 10.1093/rheumatology/kez545