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Background: Sjögren's disease (SjD) is rare in pediatric patients and presenting symptoms differ from those observed in adult SjD (adSjD) patients. Pediatric SjD (pedSjD) patients present less often with sicca complaints and more frequently with parotid gland swelling and fever 1. Due to the differences in symptoms and limited knowledge of the disease at young age, diagnosing pedSjD can be challenging. Although dysregulation of multiple immune response pathways has been shown for adSjD 2, only few studies have investigated pathophysiological mechanisms of pedSjD. Objectives: To identify potentially dysregulated molecular pathways in pedSjD patients by comparing the transcriptome of peripheral blood cells between pedSjD patients and controls. Methods: Whole blood samples from 18 patients with a clinical diagnosis of pedSjD (age of disease onset ≤16 years) and 23 age- and sex-matched controls (without immune-mediated disease) were collected in PAXgene™ Blood RNA tubes and stored at -20°C. RNA was isolated and sequenced on an Illumina NovaSeq 6000 platform. Quality control (QC) and differential gene expression analysis was performed using the DESeq2 package in RStudio. Pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Snap-frozen parotid gland biopsies were available from 10 out of 18 included pedSjD patients. In addition to whole transcriptome analysis of blood samples, expression of interferon (IFN)-stimulated genes (ISGs) was measured in blood and parotid gland biopsies with Taqman Real-Time PCR. Results: The mean age±SD of pedSjD patients at time of sample collection was 14±4 years and 78% were females. Out of 18 patients, 12 (67%) were anti-SSA/Ro positive. After QC of the transcriptome data, one control was excluded based on principle component analysis. Between pedSjD patients and controls, 247 differentially expressed genes (adj. P-valueIFITM1 and CXCL10 in parotid gland tissue correlated positively with its expression in blood (ρ=0.696, P=0.017 and ρ=0.590, P=0.073, respectively), but such correlation was not observed for other ISGs, including MX1. Conclusion: The majority of pedSjD patients showed an IFN signature in blood and parotid gland tissue. Compared to IFN-high pedSjD patients, those without an IFN signature in blood had a different clinical presentation; they were less frequently positive for autoantibodies and showed more signs of acute infection. These findings suggest that the IFN signature may aid in the diagnosis and stratification of pedSjD patients, although further research with larger groups is needed. REFERENCES: 1 Legger GE, Erdtsieck MB, de Wolff L, et al. Differences in presentation between paediatric- and adult-onset primary Sjögren's syndrome patients. Clin Exp Rheumatol. 2021;39 Suppl 133(6):85-92. 2 Verstappen GM, Gao L, Pringle S, et al. The Transcriptome of Paired Major and Minor Salivary Gland Tissue in Patients With Primary Sjögren's Syndrome. Front Immunol. 2021;12:681941. Acknowledgements: NIL. Disclosure of Interests: Hendrika Bootsma AstraZeneca, AstraZeneca, Bristol-Myers Squibb, Novartis, Galapagos, Argenx, AstraZeneca, Bristol-Myers Squibb, Argenx, Elizabeth Legger: None declared, Annie Visser: None declared, Willem Maassen: None declared, Marielle E. van Gijn: None declared, Wineke Armbrust: None declared, Frans G.M. Kroese Bristol-Myers Squibb, Argenx, Bristol-Myers Squibb, Gwenny M. Verstappen Argenx, Aurinia.
Bootsma et al. (Sat,) studied this question.