preSStige

Wider research context Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease often misdiagnosed or overlooked leading to a significant delay of diagnosis. Therefore, most of the current knowledge on the pathophysiology of pSS is derived from patients with long-standing disease. Patient symptoms, immune phenotype and glandular infiltrates at the onset of pSS are unknown and biomarkers for early diagnosis have not been evaluated so far. The "Pre-Sjögren Syndrome Targeted Immunology Evaluation (preSStige)" represents a pioneering effort aimed at uncovering the initial immunological dysregulations in pSS. Spearheaded by collaborative efforts between the Universities of Graz, Austria, and Brest, France, this interdisciplinary research initiative seeks to revolutionize the understanding and early detection of pSS. Objectives The overarching goal of the research is to discern whether identified immune system changes are root causes of pSS or mere consequences of persistent inflammation. Structured as a longitudinal cohort study, the project identifies individuals at risk for pSS (pre-Sjogren patients) and follows their progression until the development of pSS or other systemic autoimmune diseases. Presently, the study has enrolled 41 individuals, some of whom have already manifested pSS or other autoimmune diseases. Early analyses have unearthed compelling pathogenic indicators, including alterations in the naïve CD4+ T cell pool and lymphoepithelial lesions. Methods The methodology blends clinical research with cutting-edge laboratory techniques to validate and comprehend the findings. Employing advanced tools, the study conducts in-depth profiling of T, B, and NK cells. Techniques like single-cell RNA sequencing and deep learning for diagnosis prediction are integral components of the innovative research approach. Innovation: What sets this study apart is its novelty as the first longitudinal investigation involving patients before or at the clinical onset of pSS. Instead of relying on data from long-term patients with established immune system dysregulation, this research ventures into uncharted territory, studying changes in individuals as they develop the autoimmune disease. The collaboration brings together two renowned centers, each with expertise in B cells, T cells, and immune abnormalities, facilitating seamless patient recruitment. Primary researchers involved: The primary researchers leading this groundbreaking effort are Dr. Stradner and Dr. Cornec, both highly qualified rheumatologists and distinguished scientists with an extensive publication record. Their leadership extends to research teams comprising expert scientists, ensuring a comprehensive and collaborative approach to unravel the complexities of Pre-Sjögren's Syndrome.