Salivary mitochondrial RNA scores more accurately distinguished patients with Sjögren disease (SjD) from healthy controls than interferon-stimulated gene scores or plasma RNA measures, according to a recent study.
In a study published in RMD Open, researchers investigated the clinical relevance of extracellular mitochondrial RNA (mt-RNA) expression in patients with SjD, focusing on its association with interferon-stimulated gene (ISG) expression and disease activity. The research team, led by You-Jung Ha of the Seoul National University Bundang Hospital, quantified mt-RNA levels in plasma and saliva, as well as ISG expression in peripheral blood mononuclear cells (PBMCs), to evaluate their potential as biomarkers for SjD diagnosis and monitoring.
The study enrolled 111 patients with SjD who met the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) classification criteria, along with 35 healthy controls and 80 autoimmune disease controls (40 with rheumatoid arthritis [RA] and 40 with systemic lupus erythematosus). Samples of plasma, unstimulated whole saliva, and PBMCs were analyzed using quantitative real-time polymerase chain reaction to measure the expression of seven mt-RNA genes and eight ISGs. Composite mt-RNA and ISG scores were developed using multivariate logistic regression, and their discriminative abilities were assessed using receiver operating characteristic curve analyses.
Patients with SjD exhibited significantly altered mt-RNA expression compared with healthy controls. In saliva, ND1 levels were elevated, while ND5, ND6, and CYTB levels were reduced. In plasma, ND4 was increased and ND1 decreased. Saliva mt-RNA scores demonstrated strong discriminative performance, with an area under the curve (AUC) of 0.847, outperforming plasma mt-RNA scores (AUC = 0.789) and ISG scores (AUC = 0.597). Plasma mt-RNA scores were also higher in patients with SjD than in those with RA and systemic lupus erythematosus. Saliva mt-RNA scores were positively associated with objective disease activity as measured by the EULAR Sjögren Syndrome Disease Activity Index and were higher in patients with Raynaud phenomenon.
The investigators concluded that extracellular mt-RNA burden, particularly in saliva, may serve as a potential biomarker for disease diagnosis and activity in Sjögren disease. These findings suggest that mt-RNAs may contribute to immune dysregulation in SjD through mechanisms involving interferon pathway activation.
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