Identifying novel biomarkers in Sjögren's disease: insights from the Sjögren's International Collaborative Clinical Alliance

Abstract

Purpose : To identify novel biomarkers possibly capable of distinguishing Sjögren’s disease (SjD) from non-SjD.

Methods : Cross-sectional study of participants from Sjögren’s International Collaborative Clinical Alliance (SICCA) UCSF sub-cohort returning for up to 15-year follow-up. Participants were classified using the universally accepted American College of Rheumatology/European League Against Rheumatism SjD criteria. Fifteen past participants (11 SjD and 4 non-SjD) had peripheral blood collected into PAXgene RNA tubes (QIAGEN, Germantown, MD). RNA was extracted from the samples for differential gene expression. Sequenced data were quality filtered and aligned to the ENSEMBL CRCh38 human genome using hisat2. Gene count data were analyzed with DESeq2. Differentially expressed genes with false discovery rate (FDR) < 0.01 (determined using Topconfects) and with at least a 2-fold change were considered as notable. Confirmatory quantitative RT-PCRs of those identified biomarkers were then performed on a different cohort of 35 past SICCA UCSF sub-cohort participants (17 classified as SjD).

Results : The canonical interferon pathway genes OASL, SERPING1, USP18, and IFI44L were differentially expressed in the discovery cohort using unbiased RNA-seq. In the confirmatory cohort, RT-qPCR was used to show that all 4 transcripts were expressed at statistically significant higher levels in patients classified as SjD compared to patients classified as non-SjD.

Conclusions : In those classified as SjD, peripheral blood genes involved in the interferon pathway suggest that additional biomarkers may allow for distinguishing SjD from non-SjD.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.