SE RIM CHOI1, Jee-in Lee2, Yong Seok Choi3, You-Jung Ha3, Eun Ha Kang3 and Yun Jong Lee4, 1Seoul National University Bundang Hospital, Seoul, South Korea, 2Seoul National University of Bundang Hospital, Seongnam, South Korea, 3Seoul National University Bundang Hospital, Seongnam, South Korea, 4Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
Background/Purpose: Since mitochondrial double-stranded RNAs (mt-dsRNAs), an endogenous activator of interferon signaling, are elevated in primary Sjӧgren's syndrome (pSS), we evaluated their association with the expression levels of interferon-inducible genes (IFIGs) and their diagnostic performance.
Methods: One hundred four pSS patients satisfying the 2016 ACR/EULAR criteria, 14 non-SS sicca patients, and 25 healthy controls were included. Seven mt-dsRNAs levels (CYTB, ND1, CO1, ND4, CO2, ND5, and ND6) in unstimulated whole saliva (UWS) and plasma samples and 8 IFIGs (IFIT1, IFIT3, IFI44, IFI44L, LY6E, OAS1, MX1, and ISG15) levels in peripheral blood mononuclear cells (PBMCs) were measured using RT-PCR. Z-score-based standardized mt-dsRNAs and IFIGs scoring systems were constructed using multivariate logistic regressions. The area under the ROC curve (AUC), sensitivity and specificity, andYouden's index were calculated.
Results: mt-dsRNAs ND1 and ND6 in UWS and ND1 and ND4 in plasma and IFIT1, IFIT3, IFI44L, and OAS1 in PMBCs remained to be significantly associated with pSS. The mt-dsRNA score was defined as (2.16´ND1)−(1.87´ND6) in UWS and (−1.09´ND1)+(0.74´ND6) in plasma. The IFIG score in PBMC was calculated using (0.80´IFIT1)+(0.83´IFIT3)+(0.76´IFI44L) −(1.25´OAS1). Despite that they were derived from different samples, all three scores were significantly correlated mutually. The AUC of UWS (0.924) and plasma (0.874) mt-dsRNA scores were larger than that of PMBC IFIG score (0.817). With the optimal cut-off of 1.71, the sensitivity and specificity of UWS mt-dsRNA score were 97.4% and 89.7%, respectively.
Conclusion: Increased transcript levels of some mt-dsRNA in UWS and plasma were significantly associated with pSS. A novel mt-dsRNA scoring system could be a potential diagnostic marker for pSS diagnosis.
Table 1. Results of multivariate logistic regressions. UWS = unstimulated whole saliva; OR = odds ratio; CI = confidence interval; PBMC = peripheral blood mononuclear cell
Figure 1. Correlation between mt-dsRNA scores and IFIG scores (A) and ROC curves of mt-dsRNA and IFIG scores for in primary Sjӧgren’s syndrome. IFIG = interferon inducible genes; mt-dsRNA = mitochondrial double strand RNA; PBMC = peripheral blood mononuclear cell; SS = Sjӧgren’s syndrome; UWS = unstimulated whole saliva
Table 2. Diagnostic performance of mt-dsRNA and IFIG scores in Sjӧgren’s syndrome AUC = area under the curve; CI = confidence interval; IFIG = interferon inducible genes; mt-dsRNA = mitochondrial double strand RNA; PBMC = peripheral blood mononuclear cell; SS = Sjӧgren’s syndrome; UWS = unstimulated whole saliva
S. CHOI: None; J. Lee: None; Y. Choi: None; Y. Ha: None; E. Kang: None; Y. Lee: None.